Combined Role of CYP3A4 and CYP3A5 genetic variants in tacrolimus dose-adjusted trough levels: a clinical retrospective study in kidney transplant patients.

Tacrolimus, a calcineurin inhibitor with a narrow therapeutic index, requires precise dosing to optimize efficacy and minimize adverse effects in kidney transplant recipients. Although CYP3A5 genetic variants influence tacrolimus pharmacokinetics, they do not fully explain inter-individual differences. This retrospective study evaluated the combined impact of CYP3A4 [*1B (rs2740574), *1 G (rs2242480), *22 (rs35599367)] and CYP3A5 [*3 (rs776746), *6 (rs10264272), *7 (rs41303343)] genetic variants, as CYP3A phenotypes, on tacrolimus dose-adjusted trough concentrations (C0/D), in 94 Greek kidney transplant recipients at five time points during the first-year post-transplantation. Significant differences in tacrolimus C0/D ratios were observed across the groups. Group 4 (CYP3A5 expressers, carriers of CYP3A4*1B or *1 G) had consistently lower C0/D ratios compared to Groups 1 and 2 (CYP3A5 nonexpressers, carriers of CYP3A4*22 or CYP3A4 *1/*1) at multiple timepoints (p ≤ 0.022 and p ≤ 0.004, respectively). These findings suggest that CYP3A phenotypes could improve tacrolimus dosing decisions in kidney transplant recipients.