Optimization of initial tacrolimus dose using pharmacogenetic testing

Clin Pharmacol Ther. 2010 Jun;87(6):721-6. doi: 10.1038/clpt.2010.17. Epub 2010 Apr 14.


Retrospective studies have demonstrated that patients who are expressors of cytochrome P4503A5 (CYP3A5) require a higher tacrolimus dose to achieve a therapeutic trough concentration (C(0)). The aim of this study was to evaluate this effect prospectively by pretransplantation adaptation. We randomly assigned 280 renal transplant recipients to receive tacrolimus either according to CYP3A5 genotype or according to the standard daily regimen. The primary end point was the proportion of patients within the targeted C(0). Secondary end points included the number of dose modifications and the delay in achieving the targeted C(0). In the group receiving the adapted dose, a higher proportion of patients had values within the targeted C(0) at day 3 after initiation of tacrolimus (43.2% vs. 29.1%; P = 0.03); they required fewer dose modifications, and the targeted C(0) was achieved by 75% of these patients more rapidly. The clinical end points were similar in the two groups. Pharmacogenetic adaptation of the daily dose of tacrolimus is associated with improved achievement of the target C(0). Whether this improvement will affect clinical outcomes requires further evaluation.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cytochrome P-450 CYP3A / genetics*
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Graft Rejection / prevention & control
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / pharmacokinetics
  • Kidney Transplantation / methods*
  • Male
  • Middle Aged
  • Pharmacogenetics / methods
  • Prospective Studies
  • Tacrolimus / administration & dosage*
  • Tacrolimus / pharmacokinetics
  • Treatment Outcome


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