Bezafibrate-mizoribine interaction: Involvement of organic anion transporters OAT1 and OAT3 in rats

doi:10.1016/j.ejps.2015.10.008

	Bezafibrate-mizoribine interaction: Involvement of organic anion transporters OAT1 and OAT3 in rats
	Feng, Yuan 1; Wang, Changyuan 1,3; Liu, Qi 1,3; Meng, Qiang 1,3; Huo, Xiaokui 1,3; Liu, Zhihao 1,3; Sun, Pengyuan 1,3; Yang, Xiaobo 1,3; Sun, Huijun 1,3; Qin, Jianhua 2
刊名	EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
	2016
卷号	81 页码:119-128
关键词	Bezafibrate Mizoribine Transporter Oats Drug-drug Interactions Kidney
ISSN号	0928-0987
DOI	10.1016/j.ejps.2015.10.008
文献子类	Article
英文摘要	A patient with rheumatoid arthritis developed rhabdomyolysis while undergoing treatment with mizoribine concomitantly with bezafibrate. The symptoms rapidly disappeared and laboratory test results normalized when she discontinued the two drugs. The purpose of the present study was to elucidate the transporter-mediated molecular pharmacokinetic mechanisms of drug-drug interactions between bezafibrate and mizoribine. Comparing bezafibrate-mizoribine group with bezafibrate group, the T-max and C-max of bezafibrate were essentially unchanged in rats. The AUC of bezafibrate was significantly increased and t(1/2 beta) was prolonged markedly with an obviously reduction in plasma clearance and cumulative urinary excretion. The changes were similar to oral studies following intravenous co-administration. In rat kidney slices, the uptake of bezafibrate was markedly inhibited by p-aminohippurate, benzylpenicillin and probenecid but not by tetraethyl ammonium. Mizoribine not only decreased the uptake of bezafibrate, but also inhibited the uptake of p-aminohippurate and benzylpenicillin. The uptakes of bezafibrate and mizoribine were significantly higher compared to vector-HEK293 cells. The uptakes of bezafibrate and mizoribine in highest concentration were increased 1.63 and 1.46 folds in hOAT1-transfected cells, 1.43 and 1.24 folds in hOAT3-transfected cells, respectively. The K-m values of bezafibrate uptake by hOAT1/3hOAT1-/hOAT3-HEK293 K293 cells were increased 1.68 fold in hOAT1-HEK293 cell and 2.12 fold in hOAT3-HEK293 cell in the presence of mizoribine with no change of V-max. It indicated that mizoribine could inhibit the uptake of bezafibrate by hOAT1/3-HEK293 cells in a competitive way. In conclusion, OAT1 and OAT3 are the target transporters of drug-drug interactions between bezafibrate and mizoribine in pharmacokinetic aspects. (C) 2015 Elsevier B.V. All rights reserved.
WOS关键词	DRUG-DRUG INTERACTION ; ACUTE-RENAL-FAILURE ; INDUCED RHABDOMYOLYSIS ; CLINICAL PHARMACOKINETICS ; INTESTINAL-ABSORPTION ; RHEUMATOID-ARTHRITIS ; HEPATIC ELIMINATION ; ION TRANSPORTERS ; HUMAN KIDNEY ; IN-VITRO
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000367787700015
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/171446]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Qin, Jianhua
作者单位	1.Dalian Med Univ, Coll Pharm, Dept Clin Pharmacol, Dalian 116044, Peoples R China 2.Chinese Acad Sci, Dalian Inst Chem Phys, Div Biotechnol, Dalian 116023, Peoples R China 3.Dalian Med Univ, Prov Key Lab Pharmacokinet & Transport, Dalian 116044, Peoples R China
推荐引用方式 GB/T 7714	Feng, Yuan,Wang, Changyuan,Liu, Qi,et al. Bezafibrate-mizoribine interaction: Involvement of organic anion transporters OAT1 and OAT3 in rats[J]. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES,2016,81:119-128.
APA	Feng, Yuan.,Wang, Changyuan.,Liu, Qi.,Meng, Qiang.,Huo, Xiaokui.,...&Liu, Kexin.(2016).Bezafibrate-mizoribine interaction: Involvement of organic anion transporters OAT1 and OAT3 in rats.EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES,81,119-128.
MLA	Feng, Yuan,et al."Bezafibrate-mizoribine interaction: Involvement of organic anion transporters OAT1 and OAT3 in rats".EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES 81(2016):119-128.