Pharmacogenetic aspects of the use of tacrolimus in renal transplantation: recent developments and ethnic considerations

Jiangtao Tang, Louise Andrews, Teun Gelder, YY Shi, Ron van Schaik, LL (Lan Lan) Wang, Dennis Hesselink

Research output: Contribution to journalArticleAcademicpeer-review

106 Citations (Scopus)
31 Downloads (Pure)

Abstract

Introduction: Tacrolimus (Tac) is effective in preventing acute rejection but has considerable toxicity and inter-individual variability in pharmacokinetics and pharmacodynamics. Part of this is explained by polymorphisms in genes encoding Tac-metabolizing enzymes and transporters. A better understanding of Tac pharmacokinetics and pharmacodynamics may help to minimize different outcomes amongst transplant recipients by personalizing immunosuppression.Areas covered: The pharmacogenetic contribution of Tac metabolism will be examined, with a focus on recent discoveries, new developments and ethnic considerations.Expert opinion: The strongest and most consistent association in pharmacogenetics is between the CYP3A5 genotype and Tac dose requirement, with CYP3A5 expressers having a similar to 40-50% higher dose requirement compared to non-expressers. Two recent randomized-controlled clinical trials using CYP3A5 genotype, however, did not show a decrease in acute rejections nor reduced toxicity. CYP3A4*22, CYP3A4*26, and POR*28 are also associated with Tac dose requirements and may be included to provide the expected improvement of Tac therapy. Studies focusing on the intracellular drug concentrations and on calcineurin inhibitor-induced nephrotoxicity also seem promising. For all studies, however, the ethnic prevalence of genotypes should be taken into account, as this may significantly impact the effect of pre-emptive genotyping.
Original languageUndefined/Unknown
Pages (from-to)555-565
Number of pages11
JournalExpert Opinion on Drug Metabolism & Toxicology
Volume12
Issue number5
DOIs
Publication statusPublished - 2016

Research programs

  • EMC MM-01-25-01
  • EMC MM-04-39-05
  • EMC OR-01-34-01

Cite this