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首页> 中文期刊> 《南昌大学学报（医学版）》 >CYP3A4基因多态性对进食后阿托伐他汀钙药代动力学的影响

CYP3A4基因多态性对进食后阿托伐他汀钙药代动力学的影响

         
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目的：探讨 CYP3A4基因多态性对进食后阿托伐他汀钙药代动力学的影响。方法采用随机、2周期、自身交叉对照法，将16名健康受试者分为2组：A 组和 B 组，每组8人。A 组第1周期给予阿托伐他汀钙片20 mg 空腹口服；第2周期（1周后）给予高脂、高热量的配方饮食，后给予阿托伐他汀钙20 mg 用200 mL 温开水口服。B 组第1周期在给予高脂、高热量的配方饮食后给予阿托伐他汀钙片20 mg 口服；第2周期（1周后）给予阿托伐他汀钙20 mg 用200 mL 温开水口服。采用 RFLP-PCR 法对16名受试者进行全血 CYP3A4基因分型，采用 LC-MS-MS法检测16名受试者血浆中阿托伐他汀钙的血药浓度。比较 CYP3A4不同基因型个体空腹和进食后服用阿托伐他汀钙药代动力学参数的差异。结果16名受试者中，野生型 CYP3A4*1／*1（217 bp＋70 bp）8名（50．0％），突变杂合子 CYP3A4*1／*1G（287 bp＋217 bp ＋70 bp）8名（50．0％）。无 CYP3A4*1G／*1G 突变纯合子个体。16名受试者空腹服药时和进食后服药时野生型 CYP3A4*1／*1的 t1／2、Cmax、Tmax、AUC0－t、AUC0－∞、CL、Vd 与CYP3A4*1／*1G突变杂合子*1／*1比较差异无统计学意义（P ＞0．05）。结论CYP3A4基因多态性对进食产生的阿托伐他汀钙药动学特征的改变无影响。%ABSTRACT:Objective To investigate the effect of CYP3A4 gene polymorphisms on pharmaco-kinetics of atorvastatin calcium after food intake.Methods According to a paired,cross-over de-sign,16 volunteers were randomly divided into two groups:with 8 volunteers in each group.The group A was orally administered 20 mg atorvastatin calcium tablet on an empty stomach in the first cycle.After 1 week,group A was given high-fat and high-calorie formula diet and subsequent 20 mg atorvastatin calcium with 200 mL warm water in the second cycle.The group B was given high-fat and high-calorie formula diet and subsequent 20 mg atorvastatin calcium tablet in the first cycle,and 20 mg atorvastatin calcium with 200 mL warm water in the second cycle.Blood CYP3A4 genotyping was performed by RFLP-PCR.Plasma concentrations of atorvastatin calcium were detected by LC-MS-MS.The differences in pharmacokinetic parameters under fasting and postprandial states were compared among subjects with different CYP3A4 genotypes.Results A-mong the 16 healthy volunteers,wild-type CYP3A4* 1/* 1 (217 bp + 70 bp)was found in 8,and mutant-type* 1/* 1G (287 bp + 217 bp +70 bp)in 8.No mutant homozygote CYP3A4* 1G/* 1G was found in all subjects.There were no significant differences in t1/2 ,Cmax,Tmax,AUC0-t ,AUC0-∞ , CL and Vd under fasting and postprandial states between CYP3A4* 1/* 1 and t* 1/* 1G.Conclu-sion CYP3A4 gene polymorphisms have no effect on the pharmacokinetics of atorvastatin calci-um after food intake.

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