Abstract
Background
Effective immunosuppression through optimization of trough levels tacrolimus reduces post-transplant mortality rate in liver transplant cases.
Methods
Meta-analysis was carried out to evaluate how donor/recipient CYP3A5 (n = 678) and recipient ABCB1 (n = 318) genotypes influence tacrolimus pharmacokinetics till one-month of transplantation.
Results
The donor CYP3A5*3/*3 genotype exhibited higher concentration/dose (C/D) ratio of tacrolimus in week 1 (mean difference: 65.04, 95% CI: 15.30–114.79 ng/ml/mg/kg), week 2 (mean difference: 21.7, 95% CI: 12.6–30.9 ng/ml/mg/kg) and week 4 (mean difference: 43.28, 95% CI: 17.09 — 69.49 ng/ml/mg/kg) compared to *1/*1 and *1/*3 genotypes. The recipient CYP3A5 *3/*3 genotype did not showed significant difference in tacrolimus C/D ratio in week 1 compared to other two genotypes. However, week 2 (mean difference: 44.16, 95% CI: 3.68–84.65 ng/ml/mg/kg) and week 4 (mean difference: 43.74, 95% CI: 12.50–75.00 ng/ml/mg/kg) availability was higher in *3/*3 mutant recipients. However, the recipient ABCB1 3435 C > T polymorphism has no significant influence on tacrolimus pharmacokinetics till one month of transplant.
Conclusions
The donor and recipient CYP3A5*3 polymorphism influences tacrolimus pharmacokinetics in the first month post-transplantation, whereas the association with recipient ABCB1 3435 C > T is inconclusive.
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Naushad, S.M., Pavani, A., Rupasree, Y. et al. Recipient ABCB1, donor and recipient CYP3A5 genotypes influence tacrolimus pharmacokinetics in liver transplant cases. Pharmacol. Rep 71, 385–392 (2019). https://doi.org/10.1016/j.pharep.2019.01.006
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DOI: https://doi.org/10.1016/j.pharep.2019.01.006