title: CYP3A5 genotype had no impact on intrapatient variability of tacrolimus clearance in renal transplant recipients.
abstract: BACKGROUND
  The risk of long-term chronic allograft nephropathy and graft loss after kidney transplantation is increased in patients with a high intrapatient variability in the clearance of tacrolimus. CYP3A5 genotype has a significant influence on the oral bioavailability of tacrolimus and is a potential influence on variability of exposure.
  
  
  METHODS
  The study population consisted of 118 renal transplant recipients with stable renal function 12 months after transplant. The intrapatient variability of tacrolimus concentration was calculated. The patients were divided into low- and high-intraindividual variability groups using the median variability of tacrolimus clearance as the cutoff value.
  
  
  RESULTS
  No differences in baseline characteristics were observed between the expressers (n = 37) and nonexpressers (n = 81) except for ethnicity, which is in line with previous observations. Tacrolimus dose requirement was significantly higher in patients expressing CYP3A5, confirming earlier observations (P < 0.0001). However, intraindividual variability of tacrolimus clearance was not related to CYP3A5 genotype (P = 0.3331).
  
  
  CONCLUSIONS
  The intrapatient variability of tacrolimus clearance was not associated with CYP3A5 genotype in stable renal transplant recipients.
authors.affiliation: St George's, University of London, London, United Kingdom.
authors.forename: N
authors.initials: N
authors.lastname: Spierings
authors.forename: D W
authors.initials: DW
authors.lastname: Holt
authors.forename: Iain A M
authors.initials: IA
authors.lastname: MacPhee
mesh_terms: D000328:Adult; D001682:Biological Availability; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus