The influence of genetic polymorphisms in drug metabolism enzymes and transporters on the pharmacokinetics of different fluvastatin formulations

作     者：Qian Xiang Weidang Wu Nan Zhao Chuan Li Junyu Xu Lingyue Ma Xiaodan Zhang Qiufen Xie Zhuo Zhang Jiancheng Wang Weiren Xu Xia Zhao Yimin Cui Qian Xiang;Weidang Wu;Nan Zhao;Chuan Li;Junyu Xu;Lingyue Ma;Xiaodan Zhang;Qiufen Xie;Zhuo Zhang;Jiancheng Wang;Weiren Xu;Xia Zhao;Yimin Cui

作者机构：Department of PharmacyPeking University First HospitalBeijing 100034China State Key Laboratory of Drug Release Technology and PharmacokineticsTianjin Institute of Pharmaceutical ResearchTianjin 300193China School of Pharmaceutical SciencePeking UniversityBeijing 100191China 

出 版 物：《Asian Journal of Pharmaceutical Sciences》 (亚洲药物制剂科学（英文）)

年 卷 期：2020年第15卷第2期

页      面：264-272页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：This study was supported by grants from the National Key R&D Program of China(No.2016YFC0904900) National Natural Science Foundation(No.81673509 and No.81573504)of China Natural Science Foundation of Beijing Municipality(No.7171012) National Science and Technology Major Projects for“Major New Drugs Innovation and Development”of China(No.2017ZX09304028 and No.2017ZX09101001) 

主　　题：Genetic polymorphisms SLCO1B1 Fluvastatin Immediate-release Extended-release 

摘      要：The purpose of the present study was to investigate the impact of genetic polymorphism on fluvastatin *** addition,we compared the fluvastatin pharmacokinetics differences between extended-release(ER)80 mg tablet and immediate-release(IR)40 mg capsule in terms of drug metabolism enzyme and transporter genetic *** this open-label,randomized,two-period,two-treatment,crossover study(n=24),effects of ABCG2,SLCO1B1,ABCB1,CYP2C9 and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were *** administration dosage for IR 40 mg and ER 80 mg were twice and once daily,respectively,for total 7 *** samples for pharmacokinetic evaluation were taken on the 1st and 7th *** lower exposure following ER was *** ER tablets,SLCO1B1 T521C genotype correlated with AUC 0-24 of repeat doses(P=0.010).SLCO1B1 T521C genotype had no statistically significant effect on AUC 0-24 of IR capsule of fluvastatin after single or repeated *** vitro study demonstrated that when the concentration of fluvastatin was low(1μmol/l),transport velocity of fluvastatin by HEK293-OATP1B1 with SLCO1B1521TT(K m=11.4μmol/l)and with SLCO1B1521TCC(K m=15.1μmol/l)tend to be the *** suggests that the increased effect of SLCO1B1 T521C genotype on ER formulation of fluvastatin was mainly caused by lower blood *** recommend that formulation should be incorporated into future pharmacogenomics studies.