Effects of cytochrome P450 3A4 * 18B gene polymorphism on steady plasma drug concentration and lipid lowering efficacy of Simvastatin in Chinese hyperlipidemic patients
10.13699/j.cnki.1001-6821.2018.03.024
- VernacularTitle:高脂血症患者细胞色素P4503A4*18B基因多态性对辛伐他汀稳态血药浓度及其对降脂疗效的影响
- Author:
Bao-Jun WANG
1
;
Li-Rong ZHANG
;
Run-Fang FU
Author Information
1. 三门峡市中心医院药学部
- Keywords:
cytochrome P450 3A4 * 18B;
genetic polymorphism;
simvastatin tablet;
steady plasma drug concentration;
lipid lowering efficacy
- From:
The Chinese Journal of Clinical Pharmacology
2018;34(3):269-271
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the frequencies of cytochrome P450 3A4 * 18B (CYP3A4 * 18B) alleles in Chinese hypedipidemic patients were determined,and the impact of CYP3A4 * 18B genetic polymorphism on steady plasma drug concentration and lipid lowering efficacy of simvastatin.Methods A total of 115 patients with hyperlipidemia were given 20 mg of simvastatin treatment every day for four weeks.115 hyperlipidemic patients were respectively extracted 2 mL peripheral venous blood on an empty stomach before taking medicine and after dosing four weeks.CYP3A4 * 18B alleles were measured by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP),blood total cholesterol and low-density lipoprotein cholesterol were determined with fully automatic biochemical analyser.After dosing for four weeks,4 mL peripheral venous blood of 115 hyperlipidemic patients were collected,and the steady-state drug concentration of simvastatin was determined by HPLC.Results CYP3A4 * 18B genotype distribution of 115 hyperlipidemic patients accords with Hardy-Weinberg genetic balance (P ＞ 0.05),CYP3A4 * 18B allelic gene mutation rate was 41.74％.Steady plasma simvastatin concentrations of CYP3A4 * 1/* 1,CYP3A4 * 1/* 18B and CYP3A4 * 18B/* 18B groups were (4.88 ±0.44),(4.90 ± 0.38) and (4.71 ± 0.36) ng · mL-1,total cholesterols of three groups were (5.78 ±0.47),(5.84 ±0.47) and (5.82 ±0.52) inmol · L-1,low density lipoprotein cholesterols of three groups were (2.63 ±0.04),(2.60 ±0.08) and (2.58 ±0.12) mmol · L-1.Lipid-lowering efficacy and steady plasma drug concentration had no statistical difference between CYP3A4 * 1/* 1,CYP3A4 * 1/* 18B and CYP3A4 * 18B/* 18B groups (P ＞0.05).Conclusion There were no obvious effects of CYP3A4 * 18B gene polymorphism on steady state drug concentration and lipid-lowering efficacy of simvastatin in Chinese hyperlipidemic patients.
