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Stimulatory effect on the transport mediated by organic anion transporting polypeptide 2B1

Asian Journal of Pharmaceutical Sciences 2020年第2期15卷 181-191页

作者： Jiro Ogura Hiroaki Yamaguchi nariyasu mano Tohoku University Hospital Department of Pharmaceutical SciencesMiyagi 980-8574Japan

Drug-drug interaction(DDI)is one of causes of adverse drug events and can result in lifethreatening *** anion-transporting polypeptide(OATP)2B1 is a major uptake transporter in the intestine and contributes to transport various clinically used therapeutic *** intestine has a high risk of DDI,because it has a special propensity to be exposed to a high concentration of ***,understanding drug interaction mediated by OATP2B1 in the absorption process is important for the prevention of adverse drug events,including decrease in the therapeutic effect of co-administered *** drug interaction occurs through the direct inhibitory effect on transporters,including ***,some compounds such as clinically used drugs and food components have an acute stimulatory effect on transport of co-administered drugs by *** review summarizes the acute stimulatory effect on the transport mediated by OATP2B1 and discusses the mechanisms of the acute stimulatory effects of *** are two types of acute stimulatory effects,substrate-independent and-dependent interactions on OATP2B1 *** facilitating translocation of OATP2B1 to the plasma membrane is one of causes for the substrate-independent acute stimulatory *** the contrary,the substrate-dependent effect is based on the direct binding to the substrate-binding site or allosteric progesterone-binding site of OATP2B1.

关键词： OATP2B1 Drug interaction Stimulatory effect Membrane translocation Conformational change

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Prescription trends in children with pervasive developmental disorders:a claims data-based study in Japan

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World Journal of Pediatrics 2016年第4期12卷 443-449页

作者： Michihiro Satoh Taku Obara Hidekazu Nishigori Nobuhiro Ooba Yoshihiko Morikawa Mami Ishikuro Hirohito Metoki Masahiro Kikuya nariyasu mano Department of Pharmaceutical Sciences Tohoku University HospitalSendaiJapan Department of Preventive Medicine and Epidemiology Tohoku Medical Megabank OrganizationTohoku University2-1 Seiryo-choAoba-kuSendaiMiyagi 980-8575Japan Division of Molecular Epidemiology Tohoku University Graduate School of MedicineSendaiJapan Department of Obstetrics and Gynecology Tohoku University Graduate School of MedicineSendaiJapan School of Pharmacy Nihon UniversityChibaJapan Clinical Research Support Center Tokyo Metropolitan Children’s Medical CenterTokyoJapan Department of Community Medical Supports Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan

Background:The only drug approved for pervasive developmental disorders(PDD)in Japan is *** psychotropic drugs are also prescribed for offlabel use in Japan,but details regarding their prescription and use are largely *** purpose of this study was to clarify the use of drug treatment in Japanese children with ***:Data were extracted from claims data from the Japan Medical Data Center for children younger than 18 years of age who were newly diagnosed with PDD(International Classification of Diseases version 10 codes:F84)from 2005 to 2010(total of 3276 patients as of 2010).The prescription rates were presented as the percentage of PDD patients who were prescribed each ***:Prior to 2010,the prescription rates for atypical antipsychotics,other antipsychotics,psychostimulants,all other central nervous system drugs,anticovnvulsants,non-barbiturates,and Parkinson’s disease/syndrome drugs significantly increased among the Anatomical Therapeutic Chemical classifications defined as the“nervous system”(trend P≤0.02).The prescription rate for risperidone consistently increased,reaching 6.9%in 2010(trend P<0.0001),the highest rate of the surveyed drugs among the *** prescription rate for aripiprazole also increased(trend P<0.0001),reaching 1.9%in *** prescription rate for pimozide showed no annual changes,with a low rate of 0.4%in ***:Compared with pimozide,the prescription rates for risperidone,aripiprazole and other psychotropic drugs have *** safety data for these drugs in Japanese children are sparse,there is a need for future safety evaluations of these drugs in Japanese children.

关键词： autism children pervasive developmental disorders prescription

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The Peculiar Existence of Protein-Bound Unconjugated Bile Acid in the Cytoplasmic Fraction of Rat Brain

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色谱 2004年第4期22卷 346-348页

作者： mano nariyasu GOTO Takaaki GOTO Junichi Graduate School of Pharmaceutical Sciences Tohoku University Sendai 980-8578 JapanGraduate School of Pharmaceutical Sciences Tohoku University Sendai 980-8578 JapanGraduate School of Pharmaceutical Sciences Tohoku University Sendai 980-8578 Japan Department of Pharmaceutical Sciences Tohoku University Hospital Sendai 980-8574 Japan

Bile acids are synthesized in the liver from cholesterol by the action of hepatic enzymes and excreted into the small intestine via the bile duct. In the intestinal lumen, they assist lipolysis and the absorption of f... 详细信息

关键词：胆酸鹅脱氧胆酸脱氧胆酸液相色谱电喷雾质谱鼠脑细胞质蛋白质结合

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Highly Selective Molecular Recognition of Biologically Active Substances Using Liquid Phase Separation

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色谱 2003年第4期21卷 347-358页

作者： mano nariyasu ASAKAWA Naoki GOTO JunichiGraduate School of Pharmaceutical Sciences Tohoku University Graduate School of Pharmaceutical Sciences Tohoku UniversityTsukuba Research Laboratories Eisai Co. Ltd. 5-1-3 Tokodai Aobayama Sendai 980-8578 JapanTsukuba Iba raki 300-2635 JapanAobayama Sendai 980-8578 JapanDepartment of Pharmaceutical Sciences Tohoku University Hospital 1-1 Seiry o-machi Aoba-ku Sendai 980-8574 Japan

The development of new chiral stationary phases has been very important in the a ccurate analysis of drug enantiomers and their metabolites in biological samples during drug discovery and development. New chiral stationary phases have been d eveloped using conalbumin and flavoprotein from chicken egg whites, which have b een applied to a broad range of drug enantiomers. The application and characteri zation of these two chiral columns for high-performance liquid chromatograp hy have been documented. Both specific and non-specific interactions, based on the silica gel surface and linker moiety, influenced retention and chiral separa tion of solutes. Interactions between drug enantiomers and proteins, as a pseudo chiral stationary phase, were investigated with affinity capillary electrophore sis, in order to avoid the effects of non-specific interactions. The chiral dis crimination region for ketoprofen on the flavoprotein surface was concluded to c onsist of an α-helix structure. Studies with chemically modified flavoprot ein indicated that two types of interactions at the chiral discrimination region were required for chiral separation: a π-π interaction between a tryptophan residue and the aromatic ring of ketoprofen, and an ionic interaction between th e carboxyl group of ketoprofen and an amino and carboxyl group of the protein. I n the bod y, drugs and biologically active substances having a carboxyl group have been kn own to transform various metabolites such as acyl glucuronide. The acyl adenylat e has also been noted as a chemically active intermediate of coenzyme A ligation . Both the acyl adenylate and the acyl glucuronide produced protein adducts by r eacting with nucleophilic groups such as amino groups on protein molecules. To c haracterize both active intermediates and protein adducts, analytical techniques conferring highly selective molecular recognition, such as high-performance li quid chromatography and mass spectrometry, were required.

关键词：液相分离法生物活性材料分子识别共轭蛋白质手性稳定相亲和毛细管电泳手性识别

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Influence of the Meal and Genotype of CYP2C19 on the Pharmacokinetics of Proton Pump Inhibitors in Healthy Japanese Subjects

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Pharmacology & Pharmacy 2013年第6期4卷 502-509页

作者： Hirohiko Shinkai Tomoyuki Koike Miki Shimada Kenichiro Nakagawa Katsunori Iijima Yotaro Matsumoto Masamitsu Maekawa nariyasu mano Tooru Shimosegawa Department of Pharmaceutical Sciences Tohoku University Hospital Sendai Japan Department of Pharmaceutical Sciences Tohoku University Hospital Sendai Japan. Division of Gastroenterology Tohoku University Graduate School of Medicine Sendai Japan Division of Gastroenterology Tohoku University Graduate School of Medicine Sendai Japan

Objectives: To evaluate the influence of meals on the pharmacokinetics of omeprazole and rabeprazole and to investigate these PPIs with reference to CYP2C19 genotypes in healthy Japanese men. Methods: This was a randomized, open label, four-way crossover study. Twelve healthy Japanese male volunteers received a single oral dose of either 20 mg omeprazole or 10 mg rabeprazole, in the fasted state and after a standardized breakfast. Results: Between the administration of omeprazole in the fasted state and after breakfast, there were no significant differences in Cmax, AUC, Tmax, and half-life. Between the administration of rabeprazole in the fasted state and after breakfast, there were no significant differences in Cmax, AUC and half-life, whereas the Tmax of rabeprazole after breakfast was significantly delayed (2.8 ± 1.0 vs 5.3 ± 1.8 h, respectively;p = 0.006). PMs demonstrated the highest Cmax and AUC after drug intake under the fasting state and after breakfast, and homo EMs showed a significantly delayed Tmax. Conclusion: When a single dose of either PPI was administered, the pharmacokinetics of omeprazole was not affected by the meal, whereas the Tmax of rabeprazole after the meal was significantly delayed.

关键词： Proton Pump Inhibitor Omeprazole Rabeprazole CYP2C19 Pharmacokinetics

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