中国临床药理学杂志2018，Vol.34Issue(3)：269-271,3.DOI:10.13699/j.cnki.1001-6821.2018.03.024
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
Effects of cytochrome P450 3A4 * 18B gene polymorphism on steady plasma drug concentration and lipid lowering efficacy of Simvastatin in Chinese hyperlipidemic patients
汪宝军 1张莉蓉 2付润芳2
作者信息
- 1. 三门峡市中心医院药学部,河南 三门峡 472000
- 2. 郑州大学基础医学院药理学教研室,郑州 450001
- 折叠
摘要
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.关键词
细胞色素P450 3A4*18B/基因多态性/辛伐他汀片/稳态血药浓度/降脂疗效Key words
cytochrome P450 3A4 * 18B/genetic polymorphism/simvastatin tablet/steady plasma drug concentration/lipid lowering efficacy分类
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汪宝军,张莉蓉,付润芳..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[J].中国临床药理学杂志,2018,34(3):269-271,3.
