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These results suggest that PSP is secreted into the intestinal lumen by Mrp2-like transporter and that two Mrp2 substrates, PSP and pravastatin, are likely to be transported by different transport systems at the mucosal membrane. Functional analysis of phenolsulfonphthalein transport system in Long-Evans Cinnamon rats. RESULTS: The patients were divided into two groups, consisting of 52 and 54 the control and aprepitant groups, respectively, and the patient background showed no significant difference between both groups. Been a while since I created. Amazon Drive Cloud storage from Amazon.

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パッチワークの花あしらい―花のキルトとそのテクニック (こうの早苗のパッチ​ワークスタイル) on seoauditing.ru *FREE* shipping on qualifying offers. パッチ. こうの早苗のパッチワークとソーイング バッグ、キルト、ワンピース・・・ on seoauditing.ru *FREE* shipping on qualifying offers. こうの早苗のパッチワークと. Sanae Kono 'こうの早苗のパッチワーク'. Gemerkt von: Yoko Matsuda I actually love to work on the binding. It is very relaxing and gives me a sense of. rdf:type, type:図書 (Book). rdfs:label , こうの早苗のパッチワークとソーイング: バッグ、キルト、ワンピース schema:name, Kouno sanae no patchiwāku to. Title, 花のキルトワーク: こうの早苗のパッチワークスタイル. Published, ISBN, , Length, 86 pages. Export Citation, BiBTeX​.

パッチ ワーク こう の さなえ. We retrospectively evaluated the effectiveness of continuous pharmaceutical care in outpatient ICI treatment, focusing especially on the period of providing pharmaceutical recommendations.

Followers, 34 Following, Posts - See Instagram photos and videos from こうの 早苗 (@konosanae). きものをほどいて、パッチワ−ク-こうの早苗のはじめての和布. by こうの早苗 こうの早苗さんのパッチワーク・キルトの「新提案」!基本は四角形の. こうの早苗が主宰するパッチワーク専門店デ・トゥークールのオンラインショップです。こうの早苗デザインのオリジナル生地を始め、パッチワーク​キットや. Kimono o hodoite patchiwakuきものをほどいてパッチワーク Kimono o hodoite patchiwaku. こうの早苗のはじめての和布. kono sanae no. すてきにハンドメイド #こうの早苗 #マンスリーキルト #nhk出版 #デトゥークール #手芸店 #パッチワーク #キルト #konosanae #detoutcoeur #wuilt #​handmade.

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この映像は「こうの早苗のパッチワークキルト通信講座」教材用に制作された映像の一部を編集したものです。 人気作家 こうの早苗監修によるはじめての通信. キルト #パッチワーク #パッチワーク教室 #ブロードリーパース #こうの早苗 #​秋薔薇 #今日の針仕事 #今日の手仕事 #おうち時間 #やってみたいと思ってた事.パッチ ワーク こう の さなえ 老いない人生の作り方; 月のしずく; 60歳からは「小さくする」暮らし / 生き方がラクになる; きものをほどいて、パッチワーク / こうの早苗のはじめての和布. 花のキルトワーク展の作品集が届きました〜❤️ 生徒さんの作品が たーくさん載っています。 とても素晴らしい作品集になっています 言葉で伝えるのは. Time left: 5day(s) · こうの早苗 パッチワーク キット 出来上がりサイズcm四方 パンデピス デトゥークール ホビーラ. Bid: 12, JPY Time left: 21hour(s). Newly Posted; Unused. □ パッチワークに 渋めチェック生地まとめて キロ 約M こうの早苗・ハギレセット・YUWA・15枚・ベージュ・ピン. ☆こうの. こうの早苗とおうち時間を楽しもう!~EPISODE2~. こうの早苗のおうち時間. こうの早苗のおうち ChubbyMamaのカラフルパッチワーク.

パッチ ワーク こう の さなえ.

Technology profile Ff14 パッチ 4 56 ストーリームービー戦中見舞い. Thursday, 24 September , by Admin · high class glamour メンズ マイクロ パッチ · horizon view. 東北大震災の時の、 地が揺れて吾子の頭を抱え込む今何万の母 がこうする ふ えき りゅう こう「絵手紙先生」の 三面六臂山岸早苗63 名11 名園児数本年度の の力作展」 いずみ保育園 園児作品展樹脂粘土細工と木目込パッチワーク展(森.

Joy at Work: The Life-Changing Magic of Organising Your Working Life. Marie Kondo and 安藤忠雄, はたこうしろう グレイヘアのおしゃれ着こなし入門. 大沢 早苗. けーしん作品集 パッチワーク. こうの早苗(こうのさなえ)/パッチワーク・キルト/パンデピス. hyoban-​seoauditing.ru サイトの評判・評価Q&A. seoauditing.ru 退会サポートセンター.   パッチ ワーク こう の さなえ 퀼트전시회 #장충체육관 #こうの早苗 #detoutcoeur #yuwa #yuwafabric #quilt #​patchwork #sewing #handmade #퀼트 #キルト #パッチワーク #diy #손바느질. レボドパ・カルビドパ配合錠、リバスチグミンパッチmg/日が開始された。 後藤瑞子, 橋本あきら, 荻野 修, 菅原 満, 宮崎勝巳, 亀田悦子, 奥原芳子, 河野敏春, 佐藤 肺癌患者への化学療法に対する薬剤管理指導業務(2)-ワークシートの活用 廣方 玄太郎, 芳賀 早苗, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 松下 道明, 古川 博之,​. いとかず式加州清光 ダウンロード It is incredibly comprehensive and will work on all devices; if you have 2 GB CoolROM.4 devices Delta Emulator – With AltStore Step #1. Officially, GBA4iOS is. はじめてのパッチワークBOOK by 小草秧 · ちょっとだけリメイクソーイング ママの服で、ベビーウエア by 小草秧 · こうの早苗 私の好きな服 by 小草秧.

パッチ ワーク こう の さなえ

FFR PCIにこう使う. 船田 竜一. Symposium. E J. DCB summit. 座長. 足利 貴志. Bruno Scheller. Unknown history of SeQuent please. Aigan Futanari Kazehafuri 触手催眠姦 Saimin Nikubenki -Marisa Hen- 早苗さんはふたなり魔理沙 hot drops cold drops そうだ 伏見、行こう。 絵日記パッチ​ワーク11 ローズヒップとルクリリと 絵日記パッチワーク10 素直になれない超.  パッチ ワーク こう の さなえ ワーク 20こうの早苗主宰パッチワーク専門店ですパッチワーク生地パッチ​ワークキットパッチワーク用具を取り揃えています地元福岡ではパッチワーク​教室. Feeling stressed? Take a break with our guided relaxation exercises. · GIVE YOUR MIND, BODY AND SPIRIT SOME LOVE · GIVE YOUR MIND, BODY AND SPIRIT.

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パッチ ワーク こう の さなえ

Bid: 2, JPY Time left: 5day s. Bid: JPY Time left: 7day s. Bid: 2, JPY Time left: 5hour s. Bid: 1, JPY Time left: 1day s. Bid: 1, JPY Time left: 3hour s. Bid: 2, JPY Time left: 21hour s. Bid: 3, JPY Time left: 4day s. Bid: 1, JPY Time left: 4day s.

Bid: 2, JPY Time left: 3hour s. PURPOSE: There are several studies on premedication to prevent postembolization syndromes which occurs after transcatheter arterial chemoembolization TACE , but the medication to be used is still not established.

This study aimed to examine the effect of palonosetron and dexamethasone on the prevention of gastrointestinal symptoms induced by TACE. The complete response rate of antiemetic drugs and incidence and severity of gastrointestinal symptoms were compared between the antiemetic group AE group , which includes 51 patients prophylactically administered with palonosetron 0.

In the acute phase, the incidence and severity of nausea, vomiting, and anorexia significantly decreased in the AE group, but only anorexia improved in the delay phase. Additionally, postembolization syndromes, such as abdominal pain and fever, were significantly attenuated in the AE group; however, constipation worsened in this group.

Further studies will be needed to determine the most recommended 5-HT3 antagonist or dosage of dexamethasone in establishing the optimal antiemetic regimen. We also determined whether therapeutic drug monitoring of pazopanib concentrations may be used to improve its therapeutic efficacy and prevent adverse effects. Forty patients who received pazopanib for renal cancer or soft-tissue sarcoma at the Hokkaido Cancer Center were evaluated prospectively.

Cmin for pazopanib was calculated based on the measured values from the plasma samples. The efficacy and time to treatment failure were then assessed. Influence of gastrointestinal activity on the absorption of nilotinib. The purpose of this study was to evaluate the influence of gastrointestinal activity on the absorption of nilotinib.

In order to change gastrointestinal activity, mosapride was used for enhancement and butylscopolamine was used for suppression. Experiments on oral administration of nilotinib using rats whose gastrointestinal activity was altered by mosapride or butylscopolamine were carried out. The results of oral administration of acetaminophen to rats with peristalsis movement changed showed that the effects of peristalsis and gastric emptying rate GER on drug absorption could be evaluated in this experimental system.

Similarly, even with nilotinib, no change in Tmax was observed, but Cmax increased and decreased significantly. Due to the change in gastrointestinal activity, Cmax of nilotinib changed greatly. This showed that gastrointestinal activity affected the emulsifying action of bile and that the absorbability changed.

As a result of examining the contribution to the emulsifying action, it was found that when the bile does not exist in the gastrointestinal tract, absorption of nilotinib did not change even when gastrointestinal motility was enhanced.

Therefore, the results suggested that gastrointestinal activity influenced the emulsifying action of bile and the absorption of nilotinib was changed. Enhancement of intestinal absorption of coenzyme Q10 using emulsions containing oleyl polyethylene acetic acids. Emulsions have often been prepared to improve absorption of lipophilic compounds that have poor solubility.

Coenzyme Q10 CoQ10 is a lipophilic compound that has been used as an anti-aging supplement. We focused on oleyl polyethyleneoxy acetic acid, an oxa acid derivative, to prepare emulsions of CoQ10 with the expectation of application to oral pharmaceutics. Oxa acids were purified and classified into four groups based on the average length of the ethylene oxide chain. The emulsion that were prepared using the four oxa acid groups were administered to rats and the plasma concentration profiles of CoQ10 were analyzed.

The absorption of CoQ10 was improved in all emulsion groups compared with that in the powder group. The effects of oxa acids on cell viability were almost the same as those of conventional surfactants such as polyoxyethylene 20 sorbitan monooleate Tween The results showed that oxa acids are useful to prepare emulsions for oral administration and that the absorption of CoQ10 using oxa acids is significantly improved by using our formulations.

We previously reported that successive pharmaceutical care by oncology pharmacy specialists contributes to quality outpatient chemotherapy. However, there are a few reports regarding such care during immune checkpoint inhibitors ICIs treatment, despite increasing patients being treated with ICIs and the profile of immune-related adverse events being quite different from that of the adverse effects of cytotoxic agents.

We retrospectively evaluated the effectiveness of continuous pharmaceutical care in outpatient ICI treatment, focusing especially on the period of providing pharmaceutical recommendations.

The adoption rate, efficacy, and period of pharmaceutical interventions, such as prescription questions and pharmaceutical recommendations, were evaluated. A total of ICI administrations patients were evaluated. We performed face-to-face medication counseling. A total of prescription questions and pharmaceutical recommendations were conducted. Pharmaceutical recommendations were categorized into medication recommendations The adoption rate of pharmaceutical recommendations was Finally, the provision rate of pharmaceutical recommendations was significantly higher in the first 3 months after ICI treatment initiation.

We found that pharmaceutical care contributes to an improved quality of outpatient ICI treatment, and face-to-face pharmaceutical counseling up to 3 months after ICI treatment initiation is the most important. The anti-inflammatory agent colchicine may cause toxic effects such as rhabdomyolysis, pancytopenia, and acute respiratory distress syndrome in cases of overdose and when patients have renal or liver impairment.

As colchicine is a substrate for CYP3A4 and P-glycoprotein P-gp , drug-drug interactions are important factors that cause fatal colchicine-related side effects. Thus, we conducted a nation-wide survey to determine the status of inappropriate colchicine prescriptions in Japan. Patients prescribed the regular use of colchicine from April to March were identified using the Japanese large health insurance claims database. We defined these cases as "inappropriate colchicine prescriptions.

Among the enrolled patients, 43 1. These findings may be useful for medical professionals who prescribe colchicine therapy. Association of the ward pharmacy service with active implementation of therapeutic drug monitoring for vancomycin and teicoplanin-an epidemiological surveillance study using Japanese large health insurance claims database.

Background: Ward pharmacists are required for the active implementation of therapeutic drug monitoring TDM. This epidemiological study verified whether Japanese ward pharmacists contribute to improving the TDM implementation proportions of anti-methicillin-resistant Staphylococcus aureus MRSA agents using the large health insurance claims database.

In addition, implementation of TDM was identified by "the specific drug treatment management fee". To avoid confounding, the propensity score method was employed. Moreover, the clinical variables affecting TDM implementation in each anti-MRSA agent were analyzed by using a multiple logistic regression model. In contrast, no clinical variables were extracted for ABK. Validation of the usefulness of artificial neural networks for risk prediction of adverse drug reactions used for individual patients in clinical practice.

Artificial neural networks are the main tools for data mining and were inspired by the human brain and nervous system. Studies have demonstrated their usefulness in medicine. However, no studies have used artificial neural networks for the prediction of adverse drug reactions. We aimed to validate the usefulness of artificial neural networks for the prediction of adverse drug reactions and focused on vancomycin -induced nephrotoxicity.

For constructing an artificial neural network, a multilayer perceptron algorithm was employed. A fold cross validation method was adopted for evaluating the resultant artificial neural network. In total, patients who received vancomycin at Hokkaido University Hospital from November to February were enrolled. The predictive accuracy of the artificial neural network was Moreover, area under the receiver operating characteristic curve AUROC of the artificial neural network was 0. In the fold cross-validation, the accuracy obtained was The artificial neural network model predicting the vancomycin -induced nephrotoxicity showed good predictive performance.

This appears to be the first report of the usefulness of artificial neural networks for an adverse drug reactions risk prediction model. This study aimed to construct an optimal algorithm for initial dose settings of vancomycin VCM using machine learning ML with decision tree DT analysis. The study period was November to March In total, patients were included in the study. For the training group, DT analysis of the classification and regression tree algorithm was performed to construct an algorithm called DT algorithm for the initial dose settings of VCM.

As a result, the recommended daily doses ranged from In model evaluation, the DT algorithm obtained the highest rates of attaining the VCM therapeutic range compared to conventional dose-setting methods.

Therefore, our DT algorithm can be applied to clinical practice. In addition, ML is useful for setting drug doses. Some patients taking these drugs showed good therapeutic reactivity despite the disappearance of drugs from blood. We investigated whether these drugs have sustained effects even after their disappearance and whether their effects depend on their amounts of intracellular accumulation. Cell proliferation after exposure of K cells or Multidrug resistance-1 MDR-1 -transfected K cells was determined by a cell counting kit-8 assay.

The intracellular accumulation amount of the drug showing a sustained cytostatic effect was measured by ultra high performance liquid chromatography mass spectrometry. Cell viability decreased in a culture time-dependent manner after washing out nilotinib and dasatinib.

The sustained cytostatic effect of dasatinib, but not that of nilotinib, correlated with the intracellular accumulation level. In contrast, imatinib showed continuous a cytostatic effect after drug washout for long-term exposure but not after drug washout for short-term exposure.

These results suggest that a good response in patients with a low serum concentration of imatinib, nilotinib or dasatinib may be due to the cytostatic effect of that drug continues even after its disappearance in plasma.

Comparison of predictive performance of drug dose settings using renal function estimation equations based on the Japanese population: a preliminary retrospective study using vancomycin dosing data. Methods: This study was a single-center retrospective observational study.

Patients who died during the therapeutic period, patients younger than 18 years of age, and patients undergoing hemodialysis were excluded. We also investigated the time to onset and the risk factors of AKI in this population. AKI severity was mostly stage 1 in both groups. Improvement of renal function estimation equations for elderly Japanese people.

Background and aim: The Cockcroft-Gault C-G equation for estimation of creatinine clearance CCr is still used in a clinical setting for drug dosage adjustment. Because differences between measured and estimated CCr values have been reported, particularly for Japanese elderly people, the aim of this study was to improve the accuracy of CCr estimation equations, such as C-G and Orita-Horio, by fitting to newly obtained data.

Method: Data from subjects over the age of 40 years with laboratory data available were used for analysis in this study. By fitting the coefficients of the estimation equations to the present population, the mean error was reduced by almost half, particularly for people over the age of Although all the values calculated by the GFR estimation equations were underestimated compared with measured CCr due to secretion, a coefficient of determination of above 0.

Conclusions: Improvement of the fitted CCr estimation equations suggests that reconstruction of renal function estimation equations is required, especially for old people. Enhancement of lymphatic transport of lutein by oral administration of a solid dispersion and a self-microemulsifying drug delivery system.

Lutein is located in the macula lutea in the human eye. Since humans cannot synthesize lutein de novo, it must be digested as food. Some studies including our previous study showed very low absorption of lutein after oral administration.

These studies also suggested that the absorption route of lutein from the small intestine involves not only the blood but also the lymph. The aim of this study was to clarify the transfer of lutein into lymph and the tissue distribution after oral administration of a solid dispersion SD and a self-microemulsifying drug delivery system SMEDDS for improvement of the absorption.

We used thoracic lymph-cannulated rats. The absorption of lutein after oral administration of each formulation was clearly evaluated by its cumulative amount in lymph. Our data clearly showed that lutein is transferred into the lymph stream from the small intestine. Plasma and intracellular concentrations in an elderly patient with chronic myeloid leukemia receiving low-dose dasatinib therapy.

Communication education is now necessary for pharmaceutical education since the role of pharmacists has expanded from "medicine-based" to "person-based". However, a standard for assessing the effectiveness of a communication education program has not been established.

Hence, the aim of this study was to determine the effectiveness of clinical training in pharmacy for enhancing the ability of pharmacy students to communicate. Role playing with simulated patients was performed by pharmacy students before and after clinical practice for pharmacy, and the effects of learning were analyzed by Roter method of interaction process analysis RIAS. Analysis by RIAS enabled quantification and objective evaluation of communication by pharmacy students.

The results showed improvement of interactive communication, decrease of "Question asking" and "Others" including "Transition words", and increase of "Partnership behaviors" and "Counsel behaviors". The pharmacy students became skillful in communication without showing hesitation. The results therefore showed that clinical training contributes to improvement in the ability of pharmacy students to communicate.

Tocopherol is used not only as an ethical drug but also as a supplement. An approach to avoid its undesirable consequence was also examined. The inhibitory effect of ezetimibe can be prevented by an administration interval of 4 h, although ezetimibe is a medicine of enterohepatic circulation. Storage under high temperature and humid conditions has been reported to decrease the dissolution rate for some kinds of tablets containing polyvinylpolypyrrolidone PVPP as a disintegrant.

The aim of this study was to elucidate the properties of pharmaceutical formulations with PVPP that cause a decrease in the dissolution rate after storage under high temperature and humid conditions by using model tablets with a simple composition. Model tablets, which consisted of rosuvastatin calcium or 5 simple structure compounds, salicylic acid, 2-aminodipheny lmethane, 2-aminobiphenyl, 2- p-tolyl benzoic acid or 4.

Dissolution tests were carried out by the paddle method in the Japanese Pharmacopoeia 16th edition. These tablets showed significantly decreased water absorption activities after storage. In the case of tablets without lactose hydrate by replacing with cellulose, a decreased dissolution rate was not observed. Carboxyl and amino groups in the structure of the principal agent were not directly involved in the decreased dissolution.

We demonstrated that additives and structure of the principal agent were involved in the decreased in dissolution rate for tablets with PVPP. The results suggested that one of the reasons for a decreased dissolution rate was the inclusion of lactose hydrate in tablets. The results also indicated that compounds as principal agents with low affinity for PVPP may be easily affected by airborne water under high temperature and humid conditions. Pharmacokinetics and dose adjustment of etoposide administered in a medium-dose etoposide, cyclophosphamide and total body irradiation regimen before allogeneic hematopoietic stem cell transplantation.

We also carried out an in vivo study using rats to verify the dose adjustment. The pharmacokinetic parameters were estimated by using a 1-compartment model. Dietary and biliary cholesterol absorption contributes to the maintenance of tight control of cholesterol homeostasis. Cholesterol is present as mixed micelles formed by bile salts and phospholipids in the intestinal lumen.

However, the uptake mechanism of an enveloped substrate of NPC1L1 in whole lipid emulsion particles remains unclear. In this study, we investigated the uptake mechanism of a substrate of NPC1L1 in lipid emulsion particles. We also investigated whether these particles containing cholesterol can improve the intestinal absorption of other lipophilic components via NPC1L1.

On the other hand, its increased uptake was significantly inhibited by ezetimibe, a selective inhibitor of NPC1L1. These results suggested that not only cholesterol but also some components in lipid emulsion particles are taken up into enterocytes via NPC1L1. We also examined an approach to improve intestinal absorption of a poorly absorbed water-insoluble component, coenzyme Q10 CoQ10 , by this mechanism.

The uptake of CoQ10 in lipid emulsion particles containing cholesterol was significantly increased compared to that without cholesterol. Its increased uptake was significantly inhibited by ezetimibe. Though it is still not clear whether CoQ10 is a substrate of NPC1L1, there is a potential for improvement of the absorption of poorly absorbed components by lipid emulsion particles containing cholesterol. Schedule-dependent cytotoxicity of Etoposide and cyclophosphamide in P-glycoprotein-expressing human leukemic K cells.

Combination chemotherapy is often used to treat cancer. Many studies have shown schedule-dependent effects between anticancer drugs. Our previous studies showed that K cells pretreated with non-cytotoxic concentrations of 4-hydroperoxycyclophosphamide 4-HPC , which is a preactivated analog of cyclophosphamide CY , enhanced the cytotoxicity of etoposide VP The appearance of cellular resistance to anticancer drugs is a major problem in cancer chemotherapy.

P-Glycoprotein P-gp plays an important role in drug resistance, and VP is a substrate for this efflux pump. Cells in S phase are most sensitive to VP The results suggest that cell cycle arrest by 4-HPC pretreatment may be responsible for the enhanced cytotoxicity of VP The findings in this study should lead to improvements in clinical combination chemotherapy.

Emulsification using highly hydrophilic surfactants improves the absorption of orally administered coenzyme Q Coenzyme Q10 CoQ10 is an essential component in the electron-transport systems of mitochondria and bacteria and is often used as a supplementary treatment for some diseases. In this study, we investigated various preparations to improve the intestinal absorption of CoQ10 with focus on the effect of emulsification. We prepared a suspension and some emulsions with four types of surfactants and investigated the plasma concentration profile after oral administration to rats.

The absorption of CoQ10 was improved by an emulsion formulation although there was little absorption of CoQ10 when a suspension was administered. Bile and emulsion formulation are essential for absorption of CoQ When the preparations containing Tween20 polysorbate 20 sorbitan monolaurate and Tween80 polyoxyethylene 20 sorbitan monooleate were administered, plasma concentrations of CoQ10 were higher than those obtained with preparations containing Tween65 polyoxyethylene 20 sorbitan tristearate and Span20 sorbitan monolaurate.

Our study suggests that highly lipophilic compounds like CoQ10 would diffuse the unstirred water layer and would easily access the intestinal apical membrane by an emulsion containing a surfactant with a high HLB value.

Attention must be given to CoQ10 supplementation for patients whose bile is not excreted to the intestine such as patients with cholestasis. Intracellular uptake mechanism of lutein in retinal pigment epithelial cells.

It has received much attention recently due to its preventive effect on age-related macular degeneration, and it has been consumed as a supplement. However, little information about the pharmacokinetic properties of lutein is available.

Detailed knowledge of pharmacokinetic properties of lutein is needed for the development of pharmaceutics. In this study, we focused on the macular accumulation of lutein and investigated the uptake mechanism into human retinal pigment epithelial cells. The concentration of lutein was determined using an HPLC system. Estimation of the duration after methamphetamine injection using a pharmacokinetic model in suspects who caused fatal traffic accidents.

When the population parameters of drug pharmacokinetics in the human body system are known, the time-course of a certain drug in an individual can generally be estimated by pharmacokinetics. In the present two cases where methamphetamine abusers were suspected to have inflicted mortalities in traffic accidents, the time-elapse or duration immediately after methamphetamine injection to the time when the accidents occurred became points of contention.

In each case, we estimated the time-course of blood methamphetamine after the self-administration in the suspects using a 2-compartment pharmacokinetic model with known pharmacokinetic parameters from the literatures.

If the injected amount can be determined to a certain extent, it is easy to calculate the average time-elapse after injection by referring to reference values. However, there is considerable individual variability in the elimination rate based on genetic polymorphism and a considerably large error range in the estimated time-elapse results.

To minimize estimation errors in such cases, we also analyzed genotype of CYP2D6, which influenced methamphetamine metabolism. Estimation based on two time-point blood samples would usefully benefit legal authorities in passing ruling sentences in cases involving similar personalities and circumstances as those involved in the present study.

Successful transplantation of rat hearts subjected to extended cold preservation with a novel preservation solution. Since prolonged cold preservation of the heart deteriorates the outcome of heart transplantation, a more protective preservation solution is required. We therefore developed a new solution, named Dsol, and examined whether Dsol, in comparison to UW, could better inhibit myocardial injury resulting from prolonged cold preservation.

Syngeneic heterotopic heart transplantation in Lewis rats was performed after cold preservation with UW or Dsol for 24 or 36 h. Dsol significantly improved 7-day graft survival after h preservation.

After h preservation, Dsol was associated with significantly faster recovery of ATP content and less activation of calpain and caspase-3 after reperfusion. Dsol diminished graft injury significantly, as revealed by the lower levels of infarction, apoptosis, serum LDH and AST release, and graft fibrosis at 7-day. Dsol is therefore considered a better alternative to UW to ameliorate the outcome of heart transplantation.

The most effective drugs based on the type of cancer are chosen for chemotherapy. Tumor cells can be targeted at the DNA, RNA or protein level, and most of the classical anticancer drugs interact with tumor DNA in a time-dependent manner or a concentration-dependent manner. However, it has been unclear to date whether a combination therapy is carried out by using exact classification. Thus it is necessary to reclassify a great number of anticancer drugs.

We propose a new classification system based on pharmacological effects of anticancer drugs. Classification of four anticancer drugs cisplatin, carboplatin, paclitaxel and gemcitabine was performed by the 3- 4,5-Dimethylthiazolyl -2,5-diphenyl-2H-tetrazolium bromide MTT assay. The present approach may be combined to enhance the chemosensitivity, improve the dose of cytotoxic drugs and evaluate the effects of novel anticancer drugs.

The six-year pharmacy program started in April in Japan. In the new program, students in the fifth year of the pharmacy course undergo a long-term practice experience pharmacy clerkship in community pharmacy and hospital pharmacy settings as compulsory 20 course credits.

The new pharmacy practice experience started in May A start of the new system was a chance as for beginning movement, thus we conducted the questionnaire survey for the following steps. The finding obtained from our questionnaires indicated that many universities had already planned to execute new approaches, such as an advanced practice at outpatient units, an with medical students, and so on. Mutual inhibition between carvedilol enantiomers during racemate glucuronidation mediated by human liver and intestinal microsomes.

We have reported that enzyme kinetic parameters for carvedilol glucuronidation by human liver microsomes HLM differed greatly depending on the substrate form, namely, racemic carvedilol and each enantiomer.

Tell the Publisher! I'd like to read this book on Kindle Don't have a Kindle? Customer reviews. How are ratings calculated? Instead, our system considers things like how recent a review is and if the reviewer bought the item on Amazon. It also analyzes reviews to verify trustworthiness. Top reviews Most recent Top reviews. Top reviews from the United States. There are 0 reviews and 0 ratings from the United States. Top reviews from other countries. Translate all reviews to English. Vertel eens Goof, waarom verzamel je al die stoffen met plaatjes voor je quiltwinkeltje?

Voor de broderiepersequilts die quilters maken en gaan maken. En de Broderieperseworkshop van Quilt Juffie Goof? In het najaar. Wanneer en hoe dat vertel ik ergens in de komende zomermaanden. De Supergoof Quiltwinkel is open van dinsdag tot en met zaterdag van 10 tot half 1 en van half 2 tot 5 uur. Oudestraat in Kampen. Meer info is altijd te vinden op het Supergoof blog. Vandaag is It Quilters Huske open van Beautiful shabbychic retrofabrics in today!

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I'm going all out and shoving as many pentagons and hexagons as I can in the gaps. The embroidery was done by my very talented mum when she was quite young.

PHOEBEE quiltpattern usebothsides etsyshop creativebeestudios usebothbeautifulsides hoffmanfabrics beequilts broderieperse fusibleapplique quiltsinthewild floralfabric quiltlovers. The tangled mess is slowly emerging into a new quilt! Pattern in the making and papers ready! I know this just looks like a tangled mess …. XxB brigittegiblinquilts brigittegiblin patchwork quilting quilts applique broderieperse handmade handsewn epp englishpaperpiecing fabric vintagefabric frenchfabric fussycutting quiltsofinstagram hexagons hexagonquilt featheringthenestbook3 quiltbook quiltpattern patchworkbook quiltmaniaeditions dutchbasketsquilt quiltmaniabox.

Yep, I use color sometimes! Been a while since I created. Attempting dancing follies on my quilt. The love birds. On my lap tonight… therapy.. Are you joining me in this journey???? When you find the most beautiful floral fabric, well you just have to broderie perse it onto a tabletopper.. There are 2 options for the border in the kits… choose teal as pictured , or the pretty red. Train stitching …something new! Vertel eens Goof, waarom verzamel je al die stoffen met plaatjes voor je quiltwinkeltje?

Voor de broderiepersequilts die quilters maken en gaan maken. En de Broderieperseworkshop van Quilt Juffie Goof? In het najaar. Wanneer en hoe dat vertel ik ergens in de komende zomermaanden. De Supergoof Quiltwinkel is open van dinsdag tot en met zaterdag van 10 tot half 1 en van half 2 tot 5 uur. These studies also suggested that the absorption route of lutein from the small intestine involves not only the blood but also the lymph.

The aim of this study was to clarify the transfer of lutein into lymph and the tissue distribution after oral administration of a solid dispersion SD and a self-microemulsifying drug delivery system SMEDDS for improvement of the absorption. We used thoracic lymph-cannulated rats.

The absorption of lutein after oral administration of each formulation was clearly evaluated by its cumulative amount in lymph. Our data clearly showed that lutein is transferred into the lymph stream from the small intestine. Plasma and intracellular concentrations in an elderly patient with chronic myeloid leukemia receiving low-dose dasatinib therapy. Communication education is now necessary for pharmaceutical education since the role of pharmacists has expanded from "medicine-based" to "person-based".

However, a standard for assessing the effectiveness of a communication education program has not been established. Hence, the aim of this study was to determine the effectiveness of clinical training in pharmacy for enhancing the ability of pharmacy students to communicate. Role playing with simulated patients was performed by pharmacy students before and after clinical practice for pharmacy, and the effects of learning were analyzed by Roter method of interaction process analysis RIAS. Analysis by RIAS enabled quantification and objective evaluation of communication by pharmacy students.

The results showed improvement of interactive communication, decrease of "Question asking" and "Others" including "Transition words", and increase of "Partnership behaviors" and "Counsel behaviors".

The pharmacy students became skillful in communication without showing hesitation. The results therefore showed that clinical training contributes to improvement in the ability of pharmacy students to communicate. Tocopherol is used not only as an ethical drug but also as a supplement.

An approach to avoid its undesirable consequence was also examined. The inhibitory effect of ezetimibe can be prevented by an administration interval of 4 h, although ezetimibe is a medicine of enterohepatic circulation. Storage under high temperature and humid conditions has been reported to decrease the dissolution rate for some kinds of tablets containing polyvinylpolypyrrolidone PVPP as a disintegrant.

The aim of this study was to elucidate the properties of pharmaceutical formulations with PVPP that cause a decrease in the dissolution rate after storage under high temperature and humid conditions by using model tablets with a simple composition. Model tablets, which consisted of rosuvastatin calcium or 5 simple structure compounds, salicylic acid, 2-aminodipheny lmethane, 2-aminobiphenyl, 2- p-tolyl benzoic acid or 4.

Dissolution tests were carried out by the paddle method in the Japanese Pharmacopoeia 16th edition. These tablets showed significantly decreased water absorption activities after storage.

In the case of tablets without lactose hydrate by replacing with cellulose, a decreased dissolution rate was not observed. Carboxyl and amino groups in the structure of the principal agent were not directly involved in the decreased dissolution. We demonstrated that additives and structure of the principal agent were involved in the decreased in dissolution rate for tablets with PVPP.

The results suggested that one of the reasons for a decreased dissolution rate was the inclusion of lactose hydrate in tablets. The results also indicated that compounds as principal agents with low affinity for PVPP may be easily affected by airborne water under high temperature and humid conditions.

Pharmacokinetics and dose adjustment of etoposide administered in a medium-dose etoposide, cyclophosphamide and total body irradiation regimen before allogeneic hematopoietic stem cell transplantation. We also carried out an in vivo study using rats to verify the dose adjustment.

The pharmacokinetic parameters were estimated by using a 1-compartment model. Dietary and biliary cholesterol absorption contributes to the maintenance of tight control of cholesterol homeostasis. Cholesterol is present as mixed micelles formed by bile salts and phospholipids in the intestinal lumen. However, the uptake mechanism of an enveloped substrate of NPC1L1 in whole lipid emulsion particles remains unclear. In this study, we investigated the uptake mechanism of a substrate of NPC1L1 in lipid emulsion particles.

We also investigated whether these particles containing cholesterol can improve the intestinal absorption of other lipophilic components via NPC1L1. On the other hand, its increased uptake was significantly inhibited by ezetimibe, a selective inhibitor of NPC1L1. These results suggested that not only cholesterol but also some components in lipid emulsion particles are taken up into enterocytes via NPC1L1. We also examined an approach to improve intestinal absorption of a poorly absorbed water-insoluble component, coenzyme Q10 CoQ10 , by this mechanism.

The uptake of CoQ10 in lipid emulsion particles containing cholesterol was significantly increased compared to that without cholesterol.

Its increased uptake was significantly inhibited by ezetimibe. Though it is still not clear whether CoQ10 is a substrate of NPC1L1, there is a potential for improvement of the absorption of poorly absorbed components by lipid emulsion particles containing cholesterol. Schedule-dependent cytotoxicity of Etoposide and cyclophosphamide in P-glycoprotein-expressing human leukemic K cells.

Combination chemotherapy is often used to treat cancer. Many studies have shown schedule-dependent effects between anticancer drugs. Our previous studies showed that K cells pretreated with non-cytotoxic concentrations of 4-hydroperoxycyclophosphamide 4-HPC , which is a preactivated analog of cyclophosphamide CY , enhanced the cytotoxicity of etoposide VP The appearance of cellular resistance to anticancer drugs is a major problem in cancer chemotherapy.

P-Glycoprotein P-gp plays an important role in drug resistance, and VP is a substrate for this efflux pump. Cells in S phase are most sensitive to VP The results suggest that cell cycle arrest by 4-HPC pretreatment may be responsible for the enhanced cytotoxicity of VP The findings in this study should lead to improvements in clinical combination chemotherapy.

Emulsification using highly hydrophilic surfactants improves the absorption of orally administered coenzyme Q Coenzyme Q10 CoQ10 is an essential component in the electron-transport systems of mitochondria and bacteria and is often used as a supplementary treatment for some diseases. In this study, we investigated various preparations to improve the intestinal absorption of CoQ10 with focus on the effect of emulsification. We prepared a suspension and some emulsions with four types of surfactants and investigated the plasma concentration profile after oral administration to rats.

The absorption of CoQ10 was improved by an emulsion formulation although there was little absorption of CoQ10 when a suspension was administered. Bile and emulsion formulation are essential for absorption of CoQ When the preparations containing Tween20 polysorbate 20 sorbitan monolaurate and Tween80 polyoxyethylene 20 sorbitan monooleate were administered, plasma concentrations of CoQ10 were higher than those obtained with preparations containing Tween65 polyoxyethylene 20 sorbitan tristearate and Span20 sorbitan monolaurate.

Our study suggests that highly lipophilic compounds like CoQ10 would diffuse the unstirred water layer and would easily access the intestinal apical membrane by an emulsion containing a surfactant with a high HLB value.

Attention must be given to CoQ10 supplementation for patients whose bile is not excreted to the intestine such as patients with cholestasis. Intracellular uptake mechanism of lutein in retinal pigment epithelial cells. It has received much attention recently due to its preventive effect on age-related macular degeneration, and it has been consumed as a supplement.

However, little information about the pharmacokinetic properties of lutein is available. Detailed knowledge of pharmacokinetic properties of lutein is needed for the development of pharmaceutics. In this study, we focused on the macular accumulation of lutein and investigated the uptake mechanism into human retinal pigment epithelial cells. The concentration of lutein was determined using an HPLC system. Estimation of the duration after methamphetamine injection using a pharmacokinetic model in suspects who caused fatal traffic accidents.

When the population parameters of drug pharmacokinetics in the human body system are known, the time-course of a certain drug in an individual can generally be estimated by pharmacokinetics. In the present two cases where methamphetamine abusers were suspected to have inflicted mortalities in traffic accidents, the time-elapse or duration immediately after methamphetamine injection to the time when the accidents occurred became points of contention. In each case, we estimated the time-course of blood methamphetamine after the self-administration in the suspects using a 2-compartment pharmacokinetic model with known pharmacokinetic parameters from the literatures.

If the injected amount can be determined to a certain extent, it is easy to calculate the average time-elapse after injection by referring to reference values. However, there is considerable individual variability in the elimination rate based on genetic polymorphism and a considerably large error range in the estimated time-elapse results.

To minimize estimation errors in such cases, we also analyzed genotype of CYP2D6, which influenced methamphetamine metabolism. Estimation based on two time-point blood samples would usefully benefit legal authorities in passing ruling sentences in cases involving similar personalities and circumstances as those involved in the present study.

Successful transplantation of rat hearts subjected to extended cold preservation with a novel preservation solution. Since prolonged cold preservation of the heart deteriorates the outcome of heart transplantation, a more protective preservation solution is required. We therefore developed a new solution, named Dsol, and examined whether Dsol, in comparison to UW, could better inhibit myocardial injury resulting from prolonged cold preservation.

Syngeneic heterotopic heart transplantation in Lewis rats was performed after cold preservation with UW or Dsol for 24 or 36 h. Dsol significantly improved 7-day graft survival after h preservation. After h preservation, Dsol was associated with significantly faster recovery of ATP content and less activation of calpain and caspase-3 after reperfusion.

Dsol diminished graft injury significantly, as revealed by the lower levels of infarction, apoptosis, serum LDH and AST release, and graft fibrosis at 7-day. Dsol is therefore considered a better alternative to UW to ameliorate the outcome of heart transplantation. The most effective drugs based on the type of cancer are chosen for chemotherapy. Tumor cells can be targeted at the DNA, RNA or protein level, and most of the classical anticancer drugs interact with tumor DNA in a time-dependent manner or a concentration-dependent manner.

However, it has been unclear to date whether a combination therapy is carried out by using exact classification. Thus it is necessary to reclassify a great number of anticancer drugs. We propose a new classification system based on pharmacological effects of anticancer drugs. Classification of four anticancer drugs cisplatin, carboplatin, paclitaxel and gemcitabine was performed by the 3- 4,5-Dimethylthiazolyl -2,5-diphenyl-2H-tetrazolium bromide MTT assay.

The present approach may be combined to enhance the chemosensitivity, improve the dose of cytotoxic drugs and evaluate the effects of novel anticancer drugs. The six-year pharmacy program started in April in Japan. In the new program, students in the fifth year of the pharmacy course undergo a long-term practice experience pharmacy clerkship in community pharmacy and hospital pharmacy settings as compulsory 20 course credits.

The new pharmacy practice experience started in May A start of the new system was a chance as for beginning movement, thus we conducted the questionnaire survey for the following steps. The finding obtained from our questionnaires indicated that many universities had already planned to execute new approaches, such as an advanced practice at outpatient units, an with medical students, and so on. Mutual inhibition between carvedilol enantiomers during racemate glucuronidation mediated by human liver and intestinal microsomes.

We have reported that enzyme kinetic parameters for carvedilol glucuronidation by human liver microsomes HLM differed greatly depending on the substrate form, namely, racemic carvedilol and each enantiomer. These phenomena were thought to be caused by mutual inhibition between carvedilol enantiomers during racemate glucuronidation.

HLM apparently preferred metabolizing S -carvedilol to R -carvedilol in the racemate, but true activities of HLM for both glucuronidation were approximately equal. By determination of the inhibitory effects of S -carvedilol on R -carvedilol glucuronidation and vice versa, it was shown that R -carvedilol glucuronidation was more easily inhibited than was S -carvedilol glucuronidation.

However, enzyme kinetic parameters were different between the two lots of HLM used in this study, depending on the contribution ratio of UGT2B4, in which R -glucuronidation was much more easily inhibited by S -carvedilol than was S -glucuronidation by R -carvedilol.

Meanwhile, HIM preferred metabolizing R -carvedilol, and this tendency was not different between the kinds of substrate form. Involvement of cholesterol membrane transporter Niemann-Pick C1-like 1 in the intestinal absorption of lutein. The physiological importance of an orally administered compound depends on its interaction with target tissues. It is therefore important to clarify the absorption mechanism in the intestine.

Ezetimibe, a selective inhibitor of intestinal NPC1L1, is the widespread lipid-lowering agent. It is important to investigate the possibility of food-drug interactions in order to prevent undesirable and harmful clinical consequences. Lutein concentration was determined by an HPLC system. On the other hand, ATP-depletion reagents sodium fluoride and sodium azide or carbonyl cyanide m-chlorophenylhydrazone did not influence the accumulation or permeation of lutein significantly.

Schedule-dependent cytotoxicity of etoposide VP and cyclophosphamide in leukemia cell line K In allogeneic bone marrow transplantation allo-BMT in patients with leukemia, the combination of VP and cyclophosphamide CY is commonly used for the conditioning regimen.

In the present study, we demonstrated schedule-dependent cytotoxicity of VP and CY in K cells. K cells were pretreated with low concentrations 2.

It was confirmed that these concentrations did not influence cell viability. Cells subsequently exposed to 0. In contrast, there was no change in the viability of K cells pretreated with low concentrations 0. On the other hand, S arrested the cell cycle at S phase. Thymidine-synchronized cells, VP showed cell cycle specificity for cell killing from early-S to mid-S phase. On the other hand, S showed cell cycle-independent cytotoxicity. Exposure of cells to VP after S induced a greater cytotoxic effect on K cells.

The findings may lead to improvements in clinical combination chemotherapy. Protective effect of lutein after ischemia-reperfusion in the small intestine. Lutein is a carotenoid mainly found in green leafy vegetables and is located in the macula lutea in the human eye. Since humans cannot synthesise lutein de novo, it must be digested as food. There is little information about the effects of intake of lutein in tissues other than the eyes.

After 60min of reperfusion, intestinal tissue was used for analysis of Evans blue dye extravasation, lipid peroxidation and myeloperoxidase activity. Pharmacokinetic properties of lutein emulsion after oral administration to rats and effect of food intake on plasma concentration of lutein. Lutein is a carotenoid found mainly in green leafy vegetables and is located in the macula lutea in the human eye. An intake of lutein as food is needed since humans cannot synthesize it de novo.

Although lutein has received much attention recently due to its antioxidant activities, little information about the pharmacokinetic properties of lutein is available.

Lutein emulsion formulation was used and the pharmacokinetics of lutein emulsion after oral administration to rats was investigated. The bioavailability of lutein using this formulation was calculated to be 5.

It was found that a large amount of lutein was accumulated in the intestinal mucosa. The absorption of orally administered compounds in the intestine can be enhanced by interaction with food or food components. Thus, the effect of food intake on the intestinal absorption of lutein was investigated.

The plasma concentration of lutein after oral administration of the emulsion formulation was improved significantly by food intake. It is possible that the absorption of lutein in the intestine is improved significantly by some food components.

Bile acids may also play important roles in the intestinal absorption of lutein since the absorption of lipophilic compounds such as cholesterol is related to bile acids. The results of these studies should contribute to an improvement of lutein absorption and provide important information for obtaining more effective pharmacological effects of lutein.

In vitro and in vivo antioxidant properties of chlorogenic acid and caffeic acid. Dietary polyphenols are thought to be beneficial for human health as antioxidants.

Coffee beans contain a common polyphenol, chlorogenic acid. Chlorogenic acid is the ester of caffeic acid and quinic acid.

Although these polyphenols have received much attention, there is little evidence indicating a relationship between the effect and the rate of absorption. In this study, we focused on the beneficial effects of chlorogenic acid and caffeic acid, a major metabolite of chlorogenic acid.

We carried out in vitro and in vivo experiments. In the in vitro study, caffeic acid had stronger antioxidant activity than that of chlorogenic acid. The uptake of chlorogenic acid by Caco-2 cells was much less than that of caffeic acid. The physiological importance of an orally administered compound depends on its availability for intestinal absorption and subsequent interaction with target tissues. We then used an intestinal ischemia-reperfusion model to evaluate antioxidant activities in vivo.

We found that both chlorogenic acid and caffeic acid had effects on intestinal ischemia-reperfusion injury.

Since caffeic acid has a stronger antioxidant activity than that of chlorogenic acid and chlorogenic acid is hydrolyzed into caffeic acid in the intestine, it is possible that caffeic acid plays a major role in the protective effect of chlorogenic acid against ischemia-reperfusion injury.

Multidrug resistance protein 2 implicates anticancer drug-resistance to sorafenib. Sorafenib and sunitinib is a small molecule inhibitor of certain receptor tyrosine kinases, and have improved outcomes for patients with advanced renal cell carcinoma.

The present study suggest that sorafenib is a substrate for MRP2, suggesting that MRP2 may implicate drug resistance to sorafenib. Effect of 5-fluorouracil treatment on SN absorption from intestine in rats. In this study, we investigated the effect of 5-FU treatment on expression levels of drug transporters for SN transportation and SN absorption from the intestine following 5-FU treatment.

Expression levels of several drug transporters and nuclear receptors in rats after 5-FU treatment were evaluated. SN absorption from the intestine was evaluated by SN concentration levels in serum following SN injection into the intestine of 5-FU treated rats.

Mrp2 levels in the intestine were downregulated to Pretreatment with 5-FU significantly increased SN concentration in the blood 30, 60 and 90 min after SN administration. The area under the curve for SN in the 5-FU group was significantly higher than in vehicle groups. Protective effect of soy isoflavone genistein on ischemia-reperfusion in the rat small intestine.

In that study, the authors used a standard complex enteral diet and they suggested that it is important to find new nutrient formulas. Genistein has a wide spectrum of biochemical and pharmacological activities. The results suggest that genistein, a soy isoflavone, has the possibility as a new nutrient formula of enteral feeding. Penetration of linezolid into rabbit intervertebral discs and surrounding tissues.

Linezolid belongs to a new class of synthetic antimicrobial agent that is effective for a variety of methicillin-resistant Staphylococcus aureus MRSA infections including bone and joint MRSA infections, but the effectiveness of linezolid for the treatment of MRSA spine infection remains controversial. In this study, we investigated the diffusion of linezolid or vancomycin into normal rabbit spinal tissues to determine the adequacy of linezolid for the treatment of spinal infection.

These results suggest that linezolid is inadequate for the treatment of spine infection limited to the intervertebral disc, but may be effective for the treatment of infection extending into the muscle and bone marrow, such as in vertebral osteomyelitis, iliopsoas abscess, and postsurgical infection. Grapefruit juice enhance the uptake of coenzyme Q10 in the human intestinal cell-line Caco Coenzyme Q10 CoQ10 is very widely consumed by humans as a food supplement. However, CoQ10 is taken up from the intestine into the circulation at a low rate.

The absorption of compounds from the gastrointestinal tract is one of the important determinants for oral bioavailability. Secretory transport limits the Oral bioavailability of compounds. It has been reported that efflux transport of CoQ10 is mediated by P-glycoprotein P-gp in Caco-2 cells. We tried to improve intestinal absorption of CoQ10 by modulating P-gp.

C Elsevier Ltd. All rights reserved. Transport across the cell membrane is crucial in drug delivery. However, the process is complicated because nucleoside derivatives that are commonly used as anti-viral drugs are transported through two different types of specific transporters: concentrative transporters and equilibrative transporters.

Cross-disciplinary approaches involving both biological experiments and theoretical considerations are therefore necessary to study the transport of nucleoside analogues such as ribavirin. Here we constructed an experimental model system using the Xenopus laevis oocyte that expressed examples of both types of transporters: human concentrative nucleoside transporter 3 and human equilibrative transporter 1. We also performed a kinetic study.

Experimental results showed that the transport of ribavirin could be reduced by inhibiting one of the two types of transporters, which seems to be counterintuitive. We therefore designed a simple mathematical model of the dynamics of ribavirin uptake and analyzed the model behaviors using a numerical simulation. The theoretical results reproduced the experimentally observed phenomena and suggested a possible mechanism for the process.

Based on this mechanism, we predicted some potential methods for the effective uptake of ribavirin from a dynamics point of view. Regulatory mechanisms of SNAT2, an amino acid transporter, in L6 rat skeletal muscle cells by insulin, osmotic shock and amino acid deprivation.

Several studies have demonstrated that the activity of system A is upregulated by insulin, osmotic shock and amino acid deprivation. However, the mechanisms are not clear. We carried out studies using L6 rat skeletal muscle cells to clarify the mechanisms of upregulation of system A activity by insulin, osmotic shock and amino acid deprivation.

The upregulation was found to be due to an increase in Vmax, not Km. Chloroquine and wortmannin inhibited the upregulation induced by insulin stimulation and amino acid deprivation but not that induced by osmotic shock. On the other hand, cycloheximide and actinomycin D inhibited the upregulation by each stimulation. Moreover, PD and SP inhibited only amino acid deprivation-induced upregulation and SB inhibited only insulin-induced upregulation. Our findings indicate that the mechanisms of upregulation of system A activity by insulin, osmotic shock and amino acid deprivation are different in L6 cells.

Interaction of coenzyme Q10 with the intestinal drug transporter P-glycoprotein. In clinical trials, patients usually take many kinds of drugs at the same time. Thus, drug-drug interactions can often directly affect the therapeutic safety and efficacy of many drugs. Oral delivery is the most desirable means of drug administration.

Changes in the activity of drug transporters may substantially influence the absorption of administered drugs from the intestine. However, there have been a few studies on food-drug interactions involving transporters. It is important to be aware of the potential of food-drug interactions and to act in order to prevent undesirable and harmful clinical consequences.

Coenzyme Q10 CoQ10 is very widely consumed by humans as a food supplement because of its recognition by the public as an important nutrient in supporting human health. Since intestinal efflux transporter P-glycoprotein P-gp is one of the major factors in drug-drug interactions, we focused on this transporter.

We report here for the first time that CoQ10, which is widely used as a food supplement, affects the transport activity of P-gp. Functional analysis of phenolsulfonphthalein transport system in Long-Evans Cinnamon rats. It has been reported that the transport function for organic anions on the kidney is maintained in multidrug resistance-associated protein 2 Mrp2 -deficient rats.

PSP is transported by the potential-sensitive urate transport system in rat brush-border membranes. Unlike Long-Evans Agouti LEA rats, the initial uptake of PSP and urate into the renal brush-border membrane vesicles of LEC rats were not significantly enhanced in the presence of positive intravesicular potential, suggesting that the potential-sensitive urate transport system is impaired in LEC rats.

LEC rats should be useful for elucidating the potential-sensitive urate transport system in rats at the molecular level. PSP is transported by the potential-sensitive urate transport system in Tat brush-border membranes.

On the other hand, stereoselective metabolism of carvedilol by UGTs is still unclear. On the other hand, both A71S and HY mutations of UGT2B7 reduced capacity but did not affect affinity and, as a result, the efficiency of metabolism was remarkably reduced.

However, as in the case of UGT1A1, neither of the mutations affected stereoselective metabolism. Evaluation of effects of polymorphism for metabolic enzymes on pharmacokinetics of carvedilol by population pharmacokinetic analysis. The purpose of this study was to evaluate the effects of the polymorphism on pharmacokinetics of carvedilol by population pharmacokinetic analysis. Population pharmacokinetic analysis was performed using plasma concentrations from 41 patients with chronic heart failure or angina pectoris.

A one compartment pharmacokinetic model with first-order absorption for oral dosing was used to describe the concentration-versus-time data for carvedilol. We examined the effects of various clinical and genetic covariables in the regression models for clearance and volume of distribution.

The results suggested that the factors of interindividual variation for carvedilol clearance were creatinine clearance and polymorphisms of UGT2B7 and CYP2D6 in the Japanese population with heart disease. Ribavirin uptake by cultured human choriocarcinoma BeWo cells and Xenopus laevis oocytes expressing recombinant plasma membrane human nucleoside transporters.

We investigated the mechanism of the transport of ribavirin 1-beta-D-ribofuranosyl-1,2,4-trizolecarboxamide into placental epithelial cells using human choriocarcinoma BeWo cells and Xenopus oocytes expressing human nucleoside transporters. In Xenopus oocytes, influxes of ribavirin mediated by hCNT2 concentrative nucleoside transporter 2 , hCNT3 concentrative nucleoside transporter 3 , hENT1 equilibrative nucleoside transporter 1 and hENT2 equilibrative nucleoside transporter 2 were saturable, and apparent K m values were Difference between pharmacokinetics of mycophenolic acid MPA in rats and that in humans is caused by different affinities of MRP2 to a glucuronized form.

The aim of this study was to clarify the cause of the species difference. However, the magnitudes of inhibitory effects were different. The calculated IC50 values were Therefore, the difference of affinity between hMRP2 and rMrp2 is a possible mechanism of the difference of excretion ratio of MPAG between rats and human. The aim of this study was to determine whether the activity of glucuronidation has an influence on the area under the curve AUC of carvedilol and whether polymorphisms in UGTs and CYP2D6 contribute to individual variation in disposition of carvedilol in Japanese.

The use of an in vitro dissolution and absorption system to evaluate oral absorption of two weak bases in pH-independent controlled-release formulations. The aim of this study was to compare the oral absorption of two weak bases including their pH-independent controlled-release preparations using an in vitro evaluation system.

This system is able to simulate dissolution of drugs, pH change and permeation of drugs through the epithelial cell membrane in the gastrointestinal tract. Albendazole-polymers solid dispersion and pH-independent sustained-release granules of dipyridamole were prepared by using a solvent method. Elution profiles and predicted absorption of these preparations in gastric pH conditions similar to those in healthy subjects and patients with achlorhydria were compared with those of a physical mixture and commercial tablets.

When a physical mixture or commercial tablets were used, the elution profile and predicted absorption of both albendazole and dipyridamole were extremely pH-dependent. On the other hand, when a solid dispersion and granules were used, elution and predicted absorption were not affected by changes in pH of the flowing solution in a drug-dissolving vessel. These results are in agreement with the results of our previous in vivo study using gastric acidity-controlled rabbits.

Our results suggest that this in vitro system is useful for the evaluation of oral absorption of pH-independent controlled-release preparations. Phenolsulfonphthalein transport by potential-sensitive urate transport system. The purpose of this study was to elucidate the transporter-mediated secretion systems for phenolsulfonphthalein in brush-border membranes.

In human and rat renal brush-border membranes, a potential-sensitive transport system has been shown to be involved in the efflux of organic anions. The uptake of phenolsulfonphthalein into rat renal brush-border membrane vesicles was stimulated by an inside-positive membrane potential.

This potential-sensitive uptake of phenolsulfonphthalein was inhibited by probenecid, pyrazinoate and urate. Moreover, urate competitively inhibited the uptake of phenolsulfonphthalein. On the other hand, the uptake of phenolsulfonphthalein was slightly increased in the presence of an outward Cl- gradient. These results suggest that phenolsulfonphthalein has high affinity for the potential-sensitive urate transport system but has low affinity for an anion exchanger.

Structure-affinity relationship in the interactions of human organic anion transporter 1 with caffeine, theophylline, theobromine and their metabolites. It is well known that human organic anion transporter 1 hOAT1 transports many kinds of drugs, endogenous compounds, and toxins.

However, little is known about the structure-affinity relationship. The aim of this study was to elucidate the structure-affinity relationship using a series of structurally related compounds that interact with hOAT1. Inhibitory effects of xanthine- and uric acid-related compounds on the transport of p-aminohippuric acid were examined using CHO-K1 cells stably expressing hOAT1.

A significant correlation between inhibitory potency and lipophilicity of the tested uric acid-related compounds was observed. The main determinant of the affinity of xanthine-related compounds is the position of the methyl group.

On the other hand, lipophilicity is the main determinant of the affinity of uric acid-related compounds. It is well known that human organic anion transporter 1 hOAT1 transports many kinds of drugs, endogetious compounds, and toxins. V All rights reserved. Characterization of secretory intestinal transport of phenolsulfonphthalein. It is known that secretory transport limits the oral bioavailability of certain drugs. However, there is little information on the secretion of anionic compounds in the intestine.

Phenolsulfonphthalein PSP and p-aminohippuric acid PAH have been used widely as substrates for organic anion transport systems. PAH is transported in the secretory direction in the intestine.

The purpose of this study was to characterize the transport system for PSP in the intestine. In the jejunum, the serosal-to-mucosal permeation rate of PSP was significantly reduced in an ATP-depleted condition, whereas a significant difference was not observed in the ileum.

Some multidrug resistance-associated protein 2 Mrp2 inhibitors inhibited PSP permeation in the jejunum. However, pravastatin, a substrate of Mrp2, did not inhibit the PSP permeation. The jejunal secretory transport of pravastatin was significantly reduced in an ATP-depleted condition and by addition of probenecid, but PSP did not affect the jejunal permeation of pravastatin.

These results suggest that PSP is secreted into the intestinal lumen by Mrp2-like transporter and that two Mrp2 substrates, PSP and pravastatin, are likely to be transported by different transport systems at the mucosal membrane. The slc5a8 cDNA, cloned from mouse kidney, codes for a protein consisting of amino acids. In situ hybridization with sagittal sections of mouse kidney demonstrates abundant expression of the transcripts in the cortex as well as the medulla.

We conclude that slc5a8 is expressed abundantly in the kidney and that it plays a role in the active reabsorption of lactate. Comparison of urinary excretion of phenolsulfonphthalein in an animal model for Wilson's disease Long-Evans Cinnamon rats with that in normal Wistar rats: involvement of primary active organic anion transporter.

In the presence of CYA, the urinary excretion and the plasma concentrations of PSP in Wistar rats were decreased and increased, respectively. Absorption of ester prodrugs in Caco-2 and rat intestine models.

The aim of this study was to elucidate the absorption mechanism in Caco-2 and rat intestine models in order to improve the accuracy of prediction of oral absorption of ester prodrugs. Pivampicillin and cefcapene pivoxil hydrochloride CFPN-PI , ester-type oral antibiotics, were chosen as model ester prodrugs. The level of esterase activity in Caco-2 cells was lower than that measured in the rat jejunum when p-nitrophenyl acetate was used as a substrate.

Almost complete ester hydrolysis occurred before the ester prodrugs reached the basolateral side of the monolayer, and the disappearance of prodrugs was thought to be due to metabolism or transport after addition to the apical side of the monolayer.

When pivampicillin and CFPN-PI were used, the amounts of ampicillin and cefcapene CFPN produced by hydrolysis of prodrugs were increased because intracellular degradation of prodrugs resulted in intracellular accumulation. On the other hand, when ampicillin or CFPN was used, only a small amount of the drug reached the basolateral side of the monolayers and no intracellular accumulation was observed.

The permeability of CFPN-PI, the solubility of which is dependent on the acidity of gastric juice, across a Caco-2 monolayer or rat intestine, was also investigated by using an in vitro system that mimics the physiological state of the human gastrointestinal tract. It is concluded that our system may be a valuable tool for evaluation of oral absorption of ester prodrugs metabolized during permeation through the intestinal epithelium. Broader evaluation of such a system is warranted.

The variability of liver graft function and urinary 6beta-hydroxycortisol to cortisol ratio during liver regeneration in liver transplant recipients. Two liver transplant recipients one male and one female and eight healthy volunteers five males and three females were enrolled in this study. Urine samples were collected from the recipients from In the healthy volunteers, morning spot urine samples were collected at Long-Evans Cinnamon LEC rats have an abnormality similar to that observed in Wilson's disease in humans and are therefore a good animal model for the study of Wilson's disease.

LEC rats develop hereditary hepatitis and severe jaundice. Mutant animals with hyperbilirubinemia have been widely used as animal models for human diseases. Among these mutant animals, Eisai hyperbilirubinemic rats EHBR have defective biliary excretion of organic anions.

It has been reported that the transport function for organic anions on the kidney is maintained in EHBR. It is important to elucidate the relationship between organic anion secretion and Wilson's disease. A new system for the prediction of drug absorption using a pH-controlled Caco-2 model: evaluation of pH-dependent soluble drug absorption and pH-related changes in absorption. One purpose of this study was to develop a new system for the prediction of pH-dependent soluble drug absorption that takes into account the physiological condition of the gastrointestinal tract.

Another purpose was to establish several models of different gastric acidities: a normal gastric acidity model, a low gastric acidity model a model of achlorhydria , a temporarily elevated gastric acidity model a model of a case in which an acidic drug was coadministered to temporarily elevate gastric acidity in the case of low gastric acidity , a weak antacid model a model of a case in which a weak antacid drug, such as an H 2 receptor antagonist, was coadministered to temporarily elevate pH up to 6 , and a strong antacid model a model of a case in which a strong antacid drug, such as magnesium hydroxide, was coadministered to temporarily elevate pH up to 8.

These models were used to evaluate variation in pH-related absorption in humans. Dipyridamole preparation Persantin tablets and glibenclamide preparation Euglucon tablets , both poorly water-soluble and pH-dependent soluble drugs, were chosen as model drugs to determine whether absorption is altered by changes in levels of gastric acid. The extent of absorption of dipyridamole was remarkably lower when gastric pH was continuously elevated to 6.

The extent of absorption of glibenclamide increased dramatically when gastric pH temporarily increased to 8. These results are consistent with reported results obtained in clinical studies. The results suggest that pH-related variations in absorption in humans can be accurately predicted using our new system. Differential binding of disopyramide and warfarin enantiomers to human alpha 1 -acid glycoprotein variants.

They also vary in their drug binding abilities. Methods The AAG variants were separated by hydroxyapatite chromatography. The characteristics of the binding activities were examined by Scatchard plot analysis. The first five amino-terminal amino acids residues of the cyanogen bromide CNBr fragment residues of each of the separated AAG fractions were elucidated by Edman degradation.

Results Commercial AAG was separated into two main fractions. The binding affinities of both DP enantiomers in fraction 3 were significantly higher than those in fraction 2. The differences between dissociation constants Kd in fractions 2 and 3 were 5. The dissociation constant of S -DP 0. By contrast WR enantiomers had a higher binding affinity in fraction 2 than in fraction 3, the differences in dissociation constants between fractions 2 and 3 being The dissociation constant of S -WR 0.

Conclusions DP and WR enantiomers bind preferentially to fraction 3 and fraction 2, respectively. Influence of continuous venovenous haemodiafiltration on the pharmacokinetics of tacrolimus in liver transplant recipients with small-for-size grafts.

In adult-to-adult living donor liver transplantation LDLT , the graft volume is inevitably much smaller than the ideal liver mass standard liver volume for the recipient's metabolic demand. Patients with small-for-size grafts are treated with continuous venovenous haemodiafiltration CVVHD for the artificial liver support.

Three liver transplant recipients one male and two females and donors two males and one female were enrolled in this study. Blood samples from inflow port and outflow port were obtained on the first day at the start of CVVHD.

Whole-blood concentrations of tacrolimus were measured immediately using the microparticle enzyme immunoassay MEIA; Abbott Laboratories. CVVHD did not cause a decrease in the blood tacrolimus concentration. Adjustment to the dose or dosing interval is not required for patients treated with tacrolimus during CVVHD. An in vitro system for prediction of oral absorption of relatively water-soluble drugs and ester prodrugs.

We developed an in vitro system simulating the physiological condition in the gastrointestinal GI tract for prediction of oral absorption of relatively water-soluble drugs and ester prodrug pivampicillin. This evaluation system includes a drug-dissolving vessel DDV, assumed stomach , a pH adjustment vessel PAV, assumed intestine and a side-by-side diffusion chamber that is mounted by a Caco-2 monolayer, which is grown on a polycarbonate filter, or by a rat intestine between the donor and receiver compartments.

Our proposed system can accommodate large amounts of solid drugs, simulating a drastic pH change process in GI tract, that is, an orally administered solid drug is dissolved in the stomach pH and transferred to the intestine pH 6 , and that dissolution process can also be monitored.

The optimal flow rates for our system are 0. Using this system, cumulative permeations of eight relatively water-soluble drugs were compared, and these cumulative permeations indicated the ability of drug absorption in humans.

Drugs that permeated across a Caco-2 monolayer at cumulative permeation of more than 0. If the cumulative permeation across a Caco-2 monolayer is lower than 0. In the case of relatively water-soluble drugs, a good linear correlation was obtained between cumulative permeation across a Caco-2 monolayer and cumulative permeation across a rat intestine. The time course of permeation of the ester prodrug pivampicillin, which is metabolized in a Caco-2 monolayer or in a rat intestine, was also evaluated.

It stated clearly that it is also possible to predict the oral absorption of pivampicillin in humans based on the cumulative permeation across a Caco-2 monolayer or rat intestine. Our newly developed system enables more kinds of oral preparations and also pH-dependent soluble drugs to be evaluated. Major role of organic anion transporters in the uptake of phenolsulfonphthalein in the kidney. Phenolsulfonphthalein is used for testing renal function.

However, its excretion mechanism has not been elucidated. The purpose of this study was therefore to elucidate the transporter-mediated excretion system for phenolsulfonphthalein. The uptake of phenolsulfonphthalein by kidney slices was found to consist of two components. The IC50 values of rOat1 substrates were higher than those of rOat3 substrates. In the presence of cimetidine, the Eadie-Hofstee plot gave a single straight line.

The profile of the phenolsulfonphthalein uptake component in the presence of cimetidine was similar to that of the low-affinity component in the absence of cimetidine. We conclude that rOat1 and rOat3 are involved in the renal uptake of phenolsulfonphthalein and that phenolsulfonphthalein is a high-affinity substrate for rOat3 but is a relatively low-affinity substrate for rOat1.

Uptake of dipeptide and beta-lactam antibiotics by the basolateral membrane vesicles prepared from rat kidney. The transport of dipeptides and beta-lactam antibiotics across the rat renal basolateral membrane was examined.

The initial uptake of glycylsarcosine and cefadroxil by rat renal basolateral membrane vesicles was inhibited by the presence of all the di- and tripeptides and beta-lactam antibiotics that were tested in this study. However, the uptake of both substrates was not inhibited by glycine, an amino acid. The initial uptake of zwitterionic beta-lactam antibiotics, cefadroxil, cephradine, and cephalexin, was stimulated by preloaded glycylsarcosine countertransport effect.

On the other hand, the uptake of dianionic beta-lactam antibiotics, ceftibuten and cefixime, was not affected. A concentration-dependent initial uptake of glycylsarcosine and cefadroxil suggested the existence of a carrier-mediated mechanism, whereas the transport of ceftibuten did not show any saturated uptake. The transporter that participates in the permeation of dipeptides and beta-lactam antibiotics across basolateral membranes showed lower affinity than did PEPT1 and PEPT2.

This is the first study that showed an evidence for a peptide transporter, expressed in the rat renal basolateral membrane, that recognizes zwitterionic beta-lactam antibiotics using basolateral membrane vesicles isolated from normal rat kidney. Inhibitory effects of basic drugs on the sodium-dependent transport of L-alanine via system B0 in the small intestine. The uptake of L-alanine by cells that express hATB 0 human amino acid transporter B 0 was inhibited in the presence of imipramine.

When rat intestinal brush border membrane vesicles were used, several basic drugs had inhibitory effects. Inhibition was also observed in intestinal absorption evaluated by an in situ single-pass perfusion technique. However, the potencies of inhibition were different. The potency of inhibition was dependent on the lipophilicity of the drugs. Mechanism of active secretion of phenolsulfonphthalein in the liver via Mrp2 abcc2 , an organic anion transporter.

Phenolsulfonphthalein PSP has been selected as a model drug that is eliminated from both the kidney and liver in rats. Although the renal PSP transport system has been studied, few details of the biliary excretion of PSP have been reported.

We investigated the biliary excretion system for PSP in rats. Moreover, an efflux experiment using Caco-2 cells was carried out to confirm Mrp2-mediated PSP transport. Mrp2 inhibitors significantly decreased PSP efflux from Caco-2 cells. C Elsevier Science B. Age- and gender-related differences in carbohydrate concentrations of alpha1-acid glycoprotein variants and the effects of glycoforms on their drug-binding capacities. Several attempts have been made to elucidate the differences in compositions of the carbohydrate moiety and structure-function relationships such as drug-binding differences.

However, there have been few reports on age- and gender-related differences in compositions or concentrations of the carbohydrate moiety of AAG variants. The aim of this study was to clarify the age- and gender-related differences in carbohydrate concentrations and in drug-binding capacities of AAG glycoforms.

The AAG glycoforms were isolated by hydroxyapatite chromatography. The binding capacity of AAG to disopyramide DP , which is a basic drug, was determined using the ultrafiltration method. The concentrations of N-acetylneuraminic acid NeuAc and monosaccharides in AAG were determined using high-pH anion-exchange chromatography with pulsed-amperometric detection. A linear relationship between the amount of ganciclovir 0.

The relative standard deviations of all standard curves were greater than or equal to 0. The intra-assay precision for the ganciclovir and acyclovir samples were 6.

Using this method, the pharmacokinetics and removal of ganciclovir during continuous hemodiafiltration CHDF in a liver transplant recipient being treated for severe cytomegalovirus infection was investigated. The ultrafiltrate of ganciclovir was These results demonstrate that CHDF effectively removes ganciclovir. Until formal guidelines have been established, ganciclovir or acyclovir dosage should be adjusted according to the results of monitoring of plasma drug concentration.

The method described here is suitable for clinical monitoring of plasma ganciclovir or acyclovir levels in solid organ transplant recipients and for use in studies involving pharmacokinetics. Ionic strength has a greater effect than does transmembrane electric potential difference on permeation of tryptamine and indoleacetic acid across Caco-2 cells.

The effects of transmembrane electric potential difference and ionic strength on the permeation of tryptamine and indoleacetic acid across a Caco-2 cell monolayer were examined. A decrease in the transmembrane electric potential difference caused by the addition of potassium ion to the transport buffer had no effect on the permeation rate of either compound.

On the other hand, an increase in ionic strength resulted in a decrease in the permeation rate of tryptamine and an increase in the permeation rate of indoleacetic acid.

The changes in the permeation rate with changes in the ionic strength were correlated with the membrane surface potential monitored by 1-anilinonaphthalenesulfonic acid ANS , a fluorescent probe. We tested these effects using several other cationic and anionic compounds. These effects of ionic strength were found to be common to all drugs tested. The compound that showed a relatively lower permeation rate was given relatively stronger effect.

The possibility of overestimation or underestimation caused by these effects should be considered when the permeation of an ionic compound is evaluated using a cell monolayer system.