Recipient ABCB1, donor and recipient CYP3A5 genotypes influence tacrolimus pharmacokinetics in liver transplant cases.

Authors:
Shaik Mohammad Naushad
Shaik Mohammad Naushad
Nizam's Institute of Medical Sciences
India
Addepalli Pavani
Addepalli Pavani
Nizam's Institute of Medical Sciences
India
Yedluri Rupasree
Yedluri Rupasree
Nizam's Institute of Medical Sciences
India
Tajamul Hussain
Tajamul Hussain
King Saud University
Saudi Arabia
Salman A Alrokayan
Salman A Alrokayan
King Saud University
Saudi Arabia
Vijay Kumar Kutala
Vijay Kumar Kutala
Nizam's Institute of Medical Sciences
India

Pharmacol Rep 2019 Jan 11;71(3):385-392. Epub 2019 Jan 11.

Dept of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Hyderabad, India.

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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Source
http://dx.doi.org/10.1016/j.pharep.2019.01.006DOI Listing
January 2019

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