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.
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