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2014 Fiscal Year Final Research Report

Clinical pharmacokinetic study for management of drug side effects

Research Project

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Project/Area Number 23590173
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionKanazawa University

Principal Investigator

SAI Yoshimichi  金沢大学, 大学病院, 教授 (40262589)

Co-Investigator(Kenkyū-buntansha) MIYAMOTO Ken-ichi  金沢大学, 附属病院, 教授 (30100514)
NISHIMURA Tomohiro  慶應義塾大学, 薬学部, 講師 (40453518)
SAWAMOTO Kazuki  金沢大学, 附属病院, 特任助教 (80608696)
Co-Investigator(Renkei-kenkyūsha) ASAKURA Hidesaku  金沢大学, 附属病院, 准教授 (60192936)
Project Period (FY) 2011-04-28 – 2015-03-31
Keywords薬物体内動態 / 医薬品副作用 / 科学療法 / トランスポーター / 薬物代謝酵素
Outline of Final Research Achievements

We investigated hepatic uptake of gemcitabine (GEM) in rat and human. The uptake mechanism involved high- and low-affinity saturable components with Km values of micromolar and millimolar order, respectively. Our results suggested that the hepatic extraction of GEM is predominantly mediated by the low-affinity nucleoside transporter ENT2 at clinically relevant hepatic concentrations of GEM, the uptake would not be completely saturated. This is critical for hepatic arterial infusion (HAI), because saturation of hepatic uptake would result in a marked increase of GEM concentration, abrogating the advantage of HAI over i.v. administration in terms of severe adverse events. We investigated pharmacokinetics of linezorid (LZD) in rat and human. The incidence of thrombopenia was increased according to the increase of plasma concentration of LZD. We also found that long-term enteral nutrition affected that the expression of transporters and metabolic enzymes in the liver and small intestine.

Free Research Field

医療系薬学

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Published: 2016-06-03  

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