https://orcid.org/0000-0003-3301-1374
Abstract
Purpose
CYP3A5 polymorphisms have been associated with variations in the pharmacokinetics of tacrolimus (Tac) in kidney transplant patients. Our study aims to quantify how the CYP3A5 genotype influences tacrolimus trough concentrations (C0) in a Vietnamese outpatient population by selecting an appropriate population pharmacokinetic model of Tac for our patients.
Patients and Methods
The external dataset was obtained prospectively from 54 data of adult kidney transplant recipients treated at the 103 Military Hospital. All published Tac population pharmacokinetic models were systematically screened from PubMed and Scopus databases and were selected based on our patient’s available characteristics. Mean absolute prediction error (MAPE), mean prediction error, and goodness-of-fit plots were used to identify the appropriate model for finding the formula that identifies the influence of CYP3A5 genotype on the pharmacokinetic data of Vietnamese patients.
Results
The model of Zhu et al had a good predictive ability with MAPE of 19.29%. The influence of CYP3A5 genotype on tacrolimus clearance was expressed by the following formulas: . The simulation result showed that Tac C0 was significantly higher in patients not expressing CYP3A5 (p< 0.001).
Conclusion
The incorporation of the CYP3A5 phenotype into Zhu’s structural model has significantly enhanced our ability to predict Tacrolimus trough levels in the Vietnamese population. This study’s results underscore the valuable role of CYP3A5 phenotype in optimizing the forecast of Tac concentrations, offering a promising avenue to assist health-care practitioners in their clinical decision-making and ultimately advance patient care outcomes.
Ethics Approval
All methods were carried out in accordance with the Declaration of Helsinki. The study received ethical approval from the Ethics Committee in Biomedical Research 103 Military Hospital (No. 04/CNChT-HĐĐĐ). Participants were informed, and their consent was obtained for the research. All kidneys were donated voluntarily with written informed consent and these were conducted in accordance with the Declaration of Istanbul.
Acknowledgments
The authors sincerely thank the staff at 103 Military Hospital, Vietnam, for the accommodating data.
Disclosure
The authors declare no conflicts of interest in this work.