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 ∼ 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.

Calcineurin inhibitor, cytochrome P450, ethnicity, kidney, pharmacodynamics, pharmacogenetics, pharmacokinetics, tacrolimus, transplanation,
Informa Health Care
Department of Clinical Chemistry

Tang, J.T, Andrews, L.M, van Gelder, T, Shi, Y.Y, van Schaik, R.H.N, Wang, L.L, & Hesselink, D.A. (2016). Pharmacogenetic aspects of the use of tacrolimus in renal transplantation: Recent developments and ethnic considerations. Informa Health Care (Vol. 12, pp. 555–565). doi:10.1517/17425255.2016.1170808