Effects of organic anion transporting polypeptide1B1 and cytochrome P2C9 genetic polymorphism on the transportation of fluvastatin
10.13699/j.cnki.1001-6821.2014.09.013
- VernacularTitle:有机阴离子转运多肽1B1与细胞色素P2C9基因多态性对氟伐他汀转运代谢的影响
- Author:
Jing LIU
1
;
Gao-Feng JIN
;
Jin-Fang HU
;
Xing-Hua LI
;
Chun-Hua XIA
;
Hong ZHANG
;
Shi-Bo HUANG
;
Yu-Qing XIONG
Author Information
1. 南昌大学
- Keywords:
fluvastatin;
organic anion transporting polypeptide 1B1;
cytochrome P2 C9;
gene polymorphism
- From:
The Chinese Journal of Clinical Pharmacology
2014;(9):794-796
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the mechanism of organic anion trans-porting polypeptide1B1 (OATP1B1) and cytochrome P2C9 (CYP2C9 ) genetic polymorphism effect on the metabolism and transport of fluvasta-tin.Methods Build OATP1B1*1a,*5and*15 recombinant plasmid model and CYP2C9*1,*3 recombinant enzyme model to compare up-take and enzymatic kinetic parameters of fluvastatin in different models.Results The fluvastatin intake of OATP1B1*5 gene, OATP1B1*15 gene, OATP1B1*1a gene are ( 3.27 ±0.53 ), ( 6.88 ±2.01 ), (6.32 ±1.23 ) pmol· min-1· mg-1 protein.Compared with OATP1B1*1a, OATP1 B1*5 reduces the transport capacity of fluvastatin ( P <0.05 ) and OATP1B1*15 gene increases (P<0.05).The CLintof CYP2C9*3 and CYP2 C9*1 metabolizing fluvastatin are 0.42 , 1.25 ( P<0.05 ).The activities of CYP2C9*3 are lower than CYP2C9*1.Conclusion The OATP1B1 521 site and the CYP2C9 359 site might be the molecular action site of transport fluvastatin.Therefore , more attention should be payed in clinical applications to prevent damage caused by OATP 1B1 and CYP3A4 genetic polymorphism.
