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Effect of CYP3A4 Gene Polymorphisms on Pharmacokinetic Characteristics of Atorvastatin Calcium after Food Intake
Author(s): 
Pages: 28-31
Year: Issue:  2
Journal: Acta Academiae Medicinae Jiangxi

Keyword:  cytochrome P450 3A4gene polymorphismsatorvastatin calciumpharmacokinetics;
Abstract: 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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