title: CYP3A5 genotype is not related to the intrapatient variability of tacrolimus clearance.
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 of tacrolimus (Tac) clearance.
  
  
  METHODS
  To test whether this intrapatient variability is associated with an individual's CYP3A5 genotype, we measured the intrapatient variability in Tac clearance in a cohort of 208 kidney transplant recipients treated with Tac and mycophenolate mofetil.
  
  
  RESULTS
  Tac dose requirement was significantly higher in patients expressing CYP3A5. However, intraindividual variability of Tac clearance was not related to CYP3A5 genotype.
  
  
  CONCLUSIONS
  Intraindividual variability in Tac clearance is not related to CYP3A5 genotype. Other factors, including patient adherence, may explain the variability in Tac clearance within an individual patient over time.
authors.affiliation: Department of Hospital Pharmacy, Clinical Pharmacology Unit, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Nilufar
authors.initials: N
authors.lastname: Pashaee
authors.forename: Rachida
authors.initials: R
authors.lastname: Bouamar
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Hesselink
authors.forename: Joke I
authors.initials: JI
authors.lastname: Roodnat
authors.forename: Ron H N
authors.initials: RH
authors.lastname: van Schaik
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
mesh_terms: D000328:Adult; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D016559:Tacrolimus / Q000493:pharmacokinetics* / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D009173:Mycophenolic Acid; D016559:Tacrolimus