CYP3A5 genotype is not related to the intrapatient variability of tacrolimus clearance

Ther Drug Monit. 2011 Jun;33(3):369-71. doi: 10.1097/FTD.0b013e31821a7aa3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cytochrome P-450 CYP3A / genetics*
  • Cytochrome P-450 CYP3A / metabolism
  • Female
  • Genotype
  • Graft Rejection / drug therapy
  • Humans
  • Immunosuppressive Agents / pharmacokinetics*
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use
  • Tacrolimus / pharmacokinetics*
  • Tacrolimus / therapeutic use*

Substances

  • Immunosuppressive Agents
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • Mycophenolic Acid
  • Tacrolimus