Differences in Early Tacrolimus Exposure in Kidney Transplant Recipients With and Without CYP3A5 Genotype-Guided Tacrolimus Dosing.

Authors

Amy L Pasternak, Jenna Schwartz, Brett Vanderwerff, Sebastian Zöllner, Danielle J Haakinson, Mona Doshi, Jeong M Park

Published in

Clinical and translational science. Volume 19. Issue 9. Pages e70726.

Abstract

CYP3A5 genotype is a known predictor of tacrolimus dose requirements. This single-center retrospective study evaluated the impact of CYP3A5 genotype-guided dosing, implemented at our institution in 10/2023, on early tacrolimus exposure. Patients were included if they were adult kidney transplant recipients between 7/2014 and 10/2024; patients in the weight-based cohort had research CYP3A5 genotypes in the institutional research biorepository and the genotype-guided cohort had a clinical CYP3A5 genotype available at transplant. The primary outcome was time to therapeutic steady-state (TSS) and secondary outcomes included classification of trough concentration on postoperative-day (POD) 2, tacrolimus dose at TSS, and tacrolimus intrapatient variability (IPV) at 14- and 30-day post-transplant. Outcomes were also evaluated within each CYP3A5 phenotype and a per-protocol evaluation. Outcomes were compared via Mann-Whitney U, Chi-squared, or Fischer's exact tests. The median TSS was decreased in CYP3A5 normal metabolizers (6.0 days (3.0-6.0) vs. 16.0 days (8.0-16.0); p = 0.01) and CYP3A5 intermediate metabolizers had significantly fewer subtherapeutic troughs on POD2 (25.8% vs. 61.1%; p = 0.01) in the genotype-guided cohort. CYP3A5 poor metabolizers were more likely to have a subtherapeutic trough on POD2 in the genotype-guided cohort. The time below therapeutic range in the first 14 days was significantly reduced for CYP3A5 intermediate metabolizers who received per-protocol, genotype-guided dosing. The TSS dose did not differ between the cohorts but was lower than the genotype-guided protocol dosing. CYP3A5 genotype-guided dosing reduced the likelihood of early subtherapeutic exposure in CYP3A5 normal and intermediate metabolizers. Refinement of the genotype-guided dosing strategy may help further improve early tacrolimus exposure.

PMID:
42748365
Bibliographic data and abstract were imported from PubMed on 17 Sep 2026.

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