Rapid clearance of tacrolimus blood concentration triggered by variant pharmacogenes

J Clin Pharm Ther. 2022 Sep;47(9):1461-1465. doi: 10.1111/jcpt.13650. Epub 2022 Mar 27.

Abstract

What is known and objective: Tacrolimus (TAC) is an immunosuppressant with large interpatient pharmacokinetic variability and a narrow therapeutic index. We report a case of acute cellular rejection (ACR) type IB with insufficient TAC blood concentrations (TAC C0 ).

Case summary: ACR developed on the eighth postoperative day of kidney transplantation. During this period, TAC C0 were insufficient. This referred pharmacogenetic assessment disclosed the patient as a CYP3A5 expresser and CYP3A4*1B carrier. According to the genotype, higher doses of TAC, 15 mg twice daily, were administered and targeted TAC C0 were achieved.

What is new and conclusion: Our case presents an association of TAC rapid clearance and two alleles modifying greater CYP3A enzyme activity.

Keywords: CYP3A4; CYP3A5; acute cellular rejection; case report; pharmacogenetics; tacrolimus.

Publication types

  • Case Reports

MeSH terms

  • Cytochrome P-450 CYP3A / genetics
  • Genotype
  • Graft Rejection / genetics
  • Graft Rejection / prevention & control
  • Humans
  • Immunosuppressive Agents
  • Kidney Transplantation*
  • Tacrolimus*

Substances

  • Immunosuppressive Agents
  • Cytochrome P-450 CYP3A
  • Tacrolimus