| DOI: 10.29090/psa.2025.01.24.AB0741 | Pharm Sci Asia 2025; 52(1), 1-10 |
Both donor and recipient CYP3A5 gene polymorphisms represent as significant factors influencing Tacrolimus weight-dose adjusted concentration in the early phase after living donor liver transplantationDinh Dinh Chinh1, Vu Duong Anh Minh2, Le Ba Hai2, Nguyen Huu Duy2, Nguyen Thi Lien Huong2, Nguyen Duc Trung1,*
1 Department of Pharmacy, 108 Military Central Hospital, Hanoi, Vietnam
2
Department of Clinical Pharmacy, Faculty of Pharmacology & Clinical Pharmacy, Hanoi University of Pharmacy, Hanoi, Vietnam
Several factors are considered for individualized Tacrolimus (Tac) dosing in transplant patients, including CYP3A5 genotype as a major one. However, previous studies about the effect of CYP3A5 polymorphism on Tac exposure in living donor liver transplant (LDLT) patients remain inconclusive, largely due to the contribution difference of donor and recipient CYP3A5 genotypes. This study aimed to assess the combined impact of both donor and recipient CYP3A5 genetic polymorphism on Tacrolimus weight-dose adjusted trough level (C0/D) during the first 4 weeks after LDLT. This retrospective, single-center study included 65 adults LDLT patients. Patients with CYP3A5*1*1 or CYP3A5*1*3 are defined as CYP3A5 expressors (E), and those with CYP3A5*3*3 are referred to as non-expressors (N). Bayesian Model Averaging method was used to screen potential factors affecting C0/D, including recipient (R) and donor (D) CYP3A5 genotypes, graft-to-recipient weight ratio, patients’ demographic and subclinical characteristics at day 7, 14, 21 and 28 post-transplant. The selected significant factors were then analysed in multiple linear regression models to evaluate their impact on C0/D. To further explore effect of combined R-D genotype on Tac exposure, C0/D were evaluated among 4 groups (RE DE, REDN, RNDE, RNDN) at each time points. In the study population, a high prevalence of CYP3A5 expressors was witnessed, with 61.5% in recipients and 55.5% in donors. In multiple linear regression models, the effect of the recipient CYP3A5 genotype on C0/D was significantly observed throughout the timeline (p < 0.01). Significant impacts were also seen in donor CYP3A5 genotype at three out of four time points (except for day 7). Of note, RNDN group had consistently highest C0/D, meanwhile, the lowest C0/D was observed in REDE patients (p < 0.05). In conclusion, both recipient and donor CYP3A5 genetic polymorphisms influence Tac C0/D in the first 28 days after transplantation. Personalized Tac dosing after LDLT should be based on combined donor-recipient CYP3A5 genotype.
Keyword:
tacrolimus, CYP3A5 genetic polymorphism, liver transplantation, personalized medicine
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