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Effect of CYP3A5 genotypes on pharmacokinetic of tacrolimus in colombian liver transplant patients

Affiliation
Department of Pharmacology and Toxicology ,Research Group in Pharmacology and Toxicology “INFARTO” ,University of Antioquia ,Medellin ,Colombia
Lindarte, Erica Fernanda;
Affiliation
Laboratorio Integrado de Medicina Especializada (LIME) ,Facultad de Medicina ,IPS Universitaria ,Universidad de Antioquia ,Antioquia ,Colombia
De Jesus Vasquez, Gonzalo;
Affiliation
Grupo de Investigation en Genetica Medica ,University of Antioquia ,Medellin ,Colombia
Toro Rendón, Luis Guillermo;
Affiliation
Department of Pharmacology and Toxicology ,Research Group in Pharmacology and Toxicology “INFARTO” ,University of Antioquia ,Medellin ,Colombia
Zuluaga Salazar, Andrés Felipe;
Affiliation
Department of Pharmacology and Toxicology ,Research Group in Pharmacology and Toxicology “INFARTO” ,University of Antioquia ,Medellin ,Colombia
Buendia, Jefferson Antonio

Background Previous studies have reported a reduced tacrolimus dose-adjusted exposure in individuals expressing the CYP3A5*1 allele (rs 776746). However, information regarding Colombian liver transplantation patients is scarce. This study aimed to investigate the influence of CYP3A5 polymorphism on tacrolimus (TAC) pharmacokinetics in Colombian liver transplant patients. Methods This was a prospective, single-center, open-label, pharmacogenetic study in stable adult liver transplant recipients followed up between 2020 and 2022. To evaluate the longitudinal relationship between the Co/doses, dose, and Co and CYP3A5 polymorphisms, a generalized estimating equations model was used using a log-gamma distribution. Results We evaluated 16 patients who received TAC during the first 2 years after transplantation. CYP3A5*1 expression was observed 28% of patients. Patients with CYP3A5 expressors displayed lower C0 and C0/dose ratio and higher doses than those no expressors. We observed a lower C0/dose ratio in expresser recipients over 2 years of follow-up. Conclusion The expression of CYP3A5 in stable liver transplant patient appeared to have the greatest influence on tacrolimus pharmacokinetics over the first 2 years posttransplant.

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License Holder: Copyright © 2025 Lindarte, De Jesus Vasquez, Toro Rendón, Zuluaga Salazar and Buendia.

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