MDR1 haplotypes derived from exons 21 and 26 do not affect the steady-state pharmacokinetics of tacrolimus in renal transplant patients

Br J Clin Pharmacol. 2004 Nov;58(5):548-53. doi: 10.1111/j.1365-2125.2004.02182.x.

Abstract

Aim: This retrospective study investigated the influence of MDR1 haplotypes derived from the polymorphisms 2677G > T (exon 21) and 3435C > T (exon 26) on the pharmacokinetics of the immunosuppressant drug tacrolimus in 73 renal transplant patients.

Methods: Based on both variants of SNPs 2677 and 3435, four different haplotypes and eight different genotypes were identified in the study sample. Tacrolimus trough concentrations (C(0)) were compared between different SNP variants and genotypes, as well as between carriers and noncarriers of each haplotype. Additionally, CYP3A5 genotype (6956G > A) was determined.

Results: No significant differences were observed between groups. Differences in mean tacrolimus C(0) values between carriers and noncarriers of each haplotype ranged from -0.04 microg/litre (95% confidence interval: -0.53 to 0.60) to -23 microg/litre (-1.07 to 1.53). No association was found between CYP3A5*1/*3 genotype and tacrolimus Co concentractions.

Conclusion: MDR1 haplotypes derived from the SNPs 2677G > T (exon 21) and 3435C > T (exon 26) do not influence the pharmacokinetics of tacrolimus in renal transplant patients.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / genetics
  • Exons / genetics*
  • Female
  • Genes, MDR / genetics*
  • Genotype
  • Haplotypes / genetics*
  • Heterozygote
  • Homozygote
  • Humans
  • Immunosuppressive Agents / pharmacokinetics*
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Tacrolimus / pharmacokinetics*

Substances

  • Immunosuppressive Agents
  • Cytochrome P-450 Enzyme System
  • CYP3A protein, human
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • Tacrolimus