Genotype-Guided Dosing Improves Attainment of Therapeutic Troughs in CYP3A5 Normal Metabolizers After Kidney Transplantation.

CYP3A5

Patients expressing CYP3A5 metabolise tacrolimus faster and reach the target trough concentration later, hence higher starting doses.

This retrospective single-centre cohort study included 81 adult kidney transplant recipients with CYP3A5 normal or intermediate metabolizer phenotypes started on extended-release tacrolimus between November 2020 and August 2025. Forty-three received the conventional fixed dose of 4 mg daily and 38 a genotype-guided dose (8 mg for normal metabolizers, 6 mg for intermediate metabolizers). Time to a therapeutic trough ≥ 8 ng/mL was shortened in normal metabolizers (median 13 versus 25 days; P = 0.007), but not in the overall cohort. Both phenotypes in the guided group had troughs closer to target on postoperative day 3, with no increase in supratherapeutic concentrations or adverse clinical outcomes.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The signal is concrete and transferable: doubling the starting dose in CYP3A5 normal metabolizers saves close to two weeks in reaching target, with an extended-release formulation for which data were lacking. Its scope remains limited by the 81-patient sample, the single-centre retrospective design, and the absence of any demonstrated benefit on rejection or renal function, endpoints for which the study is underpowered.

Analysis by Dr Thibaut Benquey