In the present study, we aimed to investigate the effect of CYP3A4＊ 18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui volunteers. Blood samples were collected from volunteers for CYP3A4 genotypin...In the present study, we aimed to investigate the effect of CYP3A4＊ 18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui volunteers. Blood samples were collected from volunteers for CYP3A4 genotyping using a polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） assay. A pharmacokinetic study was then carried out in three groups with CYP3A4＊1/＊1 （n = 6）, CYP3A4＊1/＊18 （n = 6） and CYP3A4＊18/＊18 （n = 6） genotypes. Plasma levels of zolpidem were determined by HPLC-FLD method before and after a single oral dose of 10 mg zolpidem tartrate tablet. Significant differences were observed in the pharmacokinetic parameters of zolpidem among the three genotype groups （P〈0.05）. Compared with the CYP3A4＊1/＊1 group, the Cm,x of zolpidem in ＊1/＊18 and ＊18/＊18 groups （mean, 95% CI） was 0.89 （0.65-1.12） and 0.57 （0.47-0.66）, respectively, and the AUC0-1 in the ＊1/＊18 and ＊18/＊18 groups （mean, 95% CI） was 0.74 （0.22-1.26） and 0.61 （0.24-0.98）, respectively. There was a significant trend towards lower Cmax and AUC0-1 values of zolpidem in individuals with more CYP3A＊ 18 alleles, suggesting a gene-dosage effect. The study demonstrated that the CYP3A4＊ 18 allele played an important role in the pharmacokinetics of the zolpidem after oral administration.展开更多
基金Funds of the Chinese Army Medical Science and Technology Research"Eleventh Five-Year Plan"Project(Grant No.06G023)
文摘In the present study, we aimed to investigate the effect of CYP3A4＊ 18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui volunteers. Blood samples were collected from volunteers for CYP3A4 genotyping using a polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） assay. A pharmacokinetic study was then carried out in three groups with CYP3A4＊1/＊1 （n = 6）, CYP3A4＊1/＊18 （n = 6） and CYP3A4＊18/＊18 （n = 6） genotypes. Plasma levels of zolpidem were determined by HPLC-FLD method before and after a single oral dose of 10 mg zolpidem tartrate tablet. Significant differences were observed in the pharmacokinetic parameters of zolpidem among the three genotype groups （P〈0.05）. Compared with the CYP3A4＊1/＊1 group, the Cm,x of zolpidem in ＊1/＊18 and ＊18/＊18 groups （mean, 95% CI） was 0.89 （0.65-1.12） and 0.57 （0.47-0.66）, respectively, and the AUC0-1 in the ＊1/＊18 and ＊18/＊18 groups （mean, 95% CI） was 0.74 （0.22-1.26） and 0.61 （0.24-0.98）, respectively. There was a significant trend towards lower Cmax and AUC0-1 values of zolpidem in individuals with more CYP3A＊ 18 alleles, suggesting a gene-dosage effect. The study demonstrated that the CYP3A4＊ 18 allele played an important role in the pharmacokinetics of the zolpidem after oral administration.
