Pharmacogenetic aspects of the use of tacrolimus in renal transplantation: Recent developments and ethnic considerations
Informa Health Care , Volume 12 - Issue 5 p. 555- 565
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.
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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