Differences in CYP3A genotypes of a liver transplant recipient and the donor liver graft and adjustment of tacrolimus dose

Br J Clin Pharmacol. 2019 Aug;85(8):1852-1854. doi: 10.1111/bcp.13958. Epub 2019 Jun 12.

Abstract

Tacrolimus (Tac) is well established as main immunosuppressant in most immunosuppressive regimens in solid organ transplantation. Due to the narrow therapeutic window, pre dose Tac levels (C0) are monitored in all patients receiving Tac to reach optimal therapeutic levels. Tac is metabolized in the liver and intestine by the cytochrome P450 3A (CYP3A) isoforms CYP3A4 and CYP3A5. We present a case of an African American woman who underwent a liver transplantation in which adequate Tac levels were difficult to accomplish due to differences in cytochrome P450 3A4/5 (CYP3A4/5) polymorphisms of the transplant recipient and the donor liver graft. This case report highlights that genotyping the liver transplant recipient and the donor liver graft might provide data which could be used to predict the tacrolimus metabolism post transplantation.

Keywords: CYP3A5 polymorphism; liver transplantation; pharmacogenetics; tacrolimus; therapeutic drug monitoring.

Publication types

  • Case Reports
  • Letter

MeSH terms

  • Adult
  • Alleles
  • Allografts / metabolism*
  • Cytochrome P-450 CYP3A / genetics*
  • Cytochrome P-450 CYP3A / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Genotyping Techniques
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / pharmacokinetics
  • Liver / metabolism*
  • Liver Transplantation / adverse effects
  • Polymorphism, Single Nucleotide
  • Tacrolimus / administration & dosage*
  • Tacrolimus / pharmacokinetics
  • Transplant Recipients

Substances

  • Immunosuppressive Agents
  • Cytochrome P-450 CYP3A
  • Tacrolimus