Meta-analysis of the effect of MDR1 C3435T polymorphism on cyclosporine pharmacokinetics.
The published data revealed conflicting results of the polymorphism of MDR1 exon 26 SNP C3435T on the pharmacokinetics of cyclosporine; thus, the aim was to conduct a meta-analysis of significant magnitude to investigate the influence of SNP C3435T on the pharmacokinetics of cyclosporine. A literature search was conducted to locate the relevant papers by using the PubMed electronic source from 1997 and onwards. The pharmacokinetic parameters, including AUC(0-4), AUC(0-12), AUC(0-inf), C(max), CL/F and trough concentration (C(0)), were extracted and a meta-analysis was performed by using Stata version 9.1. A total of 14 papers concerning 1036 individuals were included in the meta-analysis. The overall results showed no major influence of SNP C3435T on the pharmacokinetic parameters, including AUC(0-4), AUC(0-inf), CL/F, C(max) and C(0), although AUC(0-12) was lower in subjects with CC genotype. A subanalysis by ethnic population showed that C(0) was lower in Caucasian individuals harbouring CC genotype. In conclusion, our meta-analysis of available studies has thus far failed to demonstrate a definitive correlation between the SNP C3435T in MDR1 gene and alterations in P-glycoprotein function that can result in altered pharmacokinetics of cyclosporine, although it was indicated in this meta-analysis that the carrier of CC genotype of the SNP C3435T of MDR1 had lower cyclosporine exposure presented as AUC(0-12) than those with at least one T allele. There seems to be ethnic differences in the relationship between the SNP C3435T of MDR1 and cyclosporine pharmacokinetics.
Jiang
Zhi-Ping
ZP
Laboratory of Clinical Pharmacology, Department of Hematology, Xiang-Ya Hospital, Central-South University, Changsha, China.
Wang
Yi-Ren
YR
Xu
Ping
P
Liu
Rong-Rong
RR
Zhao
Xie-Lan
XL
Chen
Fang-Ping
FP
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000483:Alleles; D019540:Area Under Curve; D016572:Cyclosporine / Q000493:pharmacokinetics*; D005091:Exons; D019450:Genes, MDR; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016572:Cyclosporine