Single Nucleotide Polymorphisms of CYP3A4 and CYP3A5 in Romanian Kidney Transplant Recipients: Effect on Tacrolimus Pharmacokinetics in a Single-Center Experience

Overview

Journal J Clin Med

Specialty General Medicine

Date 2024 Apr 13

PMID 38610733

Authors

Corina Andreea Rotarescu

Ion Maruntelu

Ion Rotarescu

Alexandra-Elena Constantinescu

Ileana Constantinescu

Affiliations

Soon will be listed here.

Abstract

: This study examines the impact of CYP3A4 and CYP 3A5 genotypes on tacrolimus (Tac) pharmacokinetics in Romanian kidney transplanted patients. We included 112 kidney recipients genotyped for CYP3A5*3, CYP3A4*1.001, and CYP3A4*22. Patients were categorized into poor, intermediate, rapid, and ultra-rapid metabolizers based on the functional defects linked to CYP3A variants. Predominantly male (63.4%) with an average age of 40.58 years, the cohort exhibited a high prevalence of the CYP3A4*1/*1 (86.6%) and CYP3A5*3/*3 (77.7%) genotypes. CYP3A4*1.001 and CYP3A5*1 alleles significantly influenced the Tac concentration-to-dose (C0/D) ratio in various post-transplant periods, while the CYP3A4*22 allele showed no such effect ( = 0.016, < 0.001). Stepwise regression highlighted the CYP3A4*1.001's impact in early post-transplant phases, with hematocrit and age also influencing Tac variability. : The study indicates a complex interaction of CYP3A4 and CYP3A5 genotypes on Tac metabolism, suggesting the necessity for personalized medication approaches based on genetic profiling in kidney transplant recipients.

Citing Articles

Weight, Genotype, and Voriconazole Co-administration Influence Tacrolimus Initial Dosage in Pediatric Lung Transplantation Recipients with Low Hematocrit based on a Simulation Model.

Hu K, Pan J, Qu W, He S, Yang Y, Shi H Curr Pharm Des. 2024; 30(34):2736-2748.

PMID: 39129279 DOI: 10.2174/0113816128318672240807112413.

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