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

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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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Authors and Affiliations

  1. Department of Pharmacogenomics, Sandor Lifesciences Pvt Ltd, Hyderabad, India

    Shaik Mohammad Naushad, Addepalli Pavani & Yedluri Rupasree

  2. Center of Excellence in Biotechnology Research, College of Science, King Saud University, Riyadh, Saudi Arabia

    Tajamul Hussain

  3. Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia

    Salman A. Alrokayan

  4. Department of Clinical Pharmacology and Therapeutics, Nizam’s Institute of Medical Sciences, Hyderabad, India

    Vijay Kumar Kutala

Authors
  1. Shaik Mohammad Naushad
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  2. Addepalli Pavani
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  3. Yedluri Rupasree
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  4. Tajamul Hussain
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  5. Salman A. Alrokayan
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  6. Vijay Kumar Kutala
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Correspondence to Shaik Mohammad Naushad.

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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

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