title: MDR1 haplotypes derived from exons 21 and 26 do not affect the steady-state pharmacokinetics of tacrolimus in renal transplant patients.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Clinical Pharmacology, Charite-University Medicine Berlin, Germany. ingrid.mai@charite.de
authors.forename: Ingrid
authors.initials: I
authors.lastname: Mai
authors.forename: Elke S
authors.initials: ES
authors.lastname: Perloff
authors.forename: Steffen
authors.initials: S
authors.lastname: Bauer
authors.forename: Mark
authors.initials: M
authors.lastname: Goldammer
authors.forename: Andreas
authors.initials: A
authors.lastname: Johne
authors.forename: Guido
authors.initials: G
authors.lastname: Filler
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
authors.forename: Ivar
authors.initials: I
authors.lastname: Roots
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005091:Exons / Q000235:genetics*; D005260:Female; D019450:Genes, MDR / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016559:Tacrolimus / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus