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
AIM:To investigate the evidence of homogeneous phenomenon on CYP3A5*3 MDR1-3435 and CYP3A4*18of the liver graft after living donor liver transplantation(LDLT).METHODS:We identified the proportional change of the CYP3A...AIM:To investigate the evidence of homogeneous phenomenon on CYP3A5*3 MDR1-3435 and CYP3A4*18of the liver graft after living donor liver transplantation(LDLT).METHODS:We identified the proportional change of the CYP3A5*3,MDR1-3435 and CYP3A4*18 from the peripheral blood mononuclear cell of 41 pairs recipient/donor with different genotype polymorphisms and 119liver graft biopsy samples used with the pyrosequencing technique after LDLT.Polymerase chain reaction/ligase detection reaction assay and restriction fragment length polymorphism was employed for genotyping the CYP3A5*3 and CYP3A4*18 single nucleotide poly-morphisms(SNPs).All of the recipients and donors expressed with the similar SNP genotype of CYP3A5*3,MDR1-3435 or CYP3A4*18 were excluded.RESULTS:The final genetic polymorphisms of the liver graft biopsy samples of CYP3A5*3,MDR1-3435 and CYP3A4*18 was predominated depends on the donor with restriction fragment length polymorphism and seems to be less related to the recipient.The proportional changes of G to A alleles of the 119 samples of CYP3A5*3(included A】A/G,A/G】A,A/G】G,G】A,G】A/G and A】G),C to T alleles of the 108 samples of MDR1-3435(included C】C/T,C/T】C,C/T】T,T】C/T and T】C),and T to C alleles of 15 samples of CYP3A4*18(included T/C】T and T】C/T)were significant different between the recipients and the liver graft biopsy samples(P【0.0001)and less difference when compared with the donors in the pyrosequencing analysis after LDLT.CONCLUSION:The CYP3A5*3,MDR1-3435 and CYP3A4*18 of the recipient could be modified by the donor so-called homogenous phenomenon when the recipient’s blood drained into the liver graft.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.
基金Supported by A grant from Chang Gung Memorial Hospital,CMRPG8A0631 to Chiu KW of Taiwan
文摘AIM:To investigate the evidence of homogeneous phenomenon on CYP3A5*3 MDR1-3435 and CYP3A4*18of the liver graft after living donor liver transplantation(LDLT).METHODS:We identified the proportional change of the CYP3A5*3,MDR1-3435 and CYP3A4*18 from the peripheral blood mononuclear cell of 41 pairs recipient/donor with different genotype polymorphisms and 119liver graft biopsy samples used with the pyrosequencing technique after LDLT.Polymerase chain reaction/ligase detection reaction assay and restriction fragment length polymorphism was employed for genotyping the CYP3A5*3 and CYP3A4*18 single nucleotide poly-morphisms(SNPs).All of the recipients and donors expressed with the similar SNP genotype of CYP3A5*3,MDR1-3435 or CYP3A4*18 were excluded.RESULTS:The final genetic polymorphisms of the liver graft biopsy samples of CYP3A5*3,MDR1-3435 and CYP3A4*18 was predominated depends on the donor with restriction fragment length polymorphism and seems to be less related to the recipient.The proportional changes of G to A alleles of the 119 samples of CYP3A5*3(included A】A/G,A/G】A,A/G】G,G】A,G】A/G and A】G),C to T alleles of the 108 samples of MDR1-3435(included C】C/T,C/T】C,C/T】T,T】C/T and T】C),and T to C alleles of 15 samples of CYP3A4*18(included T/C】T and T】C/T)were significant different between the recipients and the liver graft biopsy samples(P【0.0001)and less difference when compared with the donors in the pyrosequencing analysis after LDLT.CONCLUSION:The CYP3A5*3,MDR1-3435 and CYP3A4*18 of the recipient could be modified by the donor so-called homogenous phenomenon when the recipient’s blood drained into the liver graft.
