Multidrug resistance gene-1 (MDR-1) haplotypes have a minor influence on tacrolimus dose requirements.

摘要: P-glycoprotein (P-gp) and the drug metabolizing enzymes have major pharmacokinetic effects. Variability in tacrolimus absorption is influenced by P-gp activity which, turn, affected single nucleotide polymorphisms (SNPs) within multidrug resistance-1 gene (MDR-1). Tacrolimus dose requirements of 206 stable renal transplant patients were related to MDR-1 genotypes SNPs C1236T, G2677T/A C3435T, as well haplotypes: C-G-C T-T-T. Lower dose-normalized blood concentrations achieved for: 2677-GG genotype patients, compared 2677-TT, for 3435-CC 3435-TT patients. There was a small, but significant, difference between haplotypes T-T-T which not significant when subclassified producers non-producers cytochrome P450 3A5 (CYP3A5). The activities CYP3A5 been shown influence bioavailability several drugs. Our data suggest that relatively minor association with pharmacokinetics.