Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Frequency of CYP3A5 Genetic Polymorphisms and Tacrolimus Pharmacokinetics in Pediatric Liver Transplantation

Version 1 : Received: 17 February 2019 / Approved: 18 February 2019 / Online: 18 February 2019 (09:14:34 CET)

A peer-reviewed article of this Preprint also exists.

Buendía, J.A.; Halac, E.; Bosaleh, A.; Garcia de Davila, M.T.; Imvertasa, O.; Bramuglia, G. Frequency of CYP3A5 Genetic Polymorphisms and Tacrolimus Pharmacokinetics in Pediatric Liver Transplantation. Pharmaceutics 2020, 12, 898. Buendía, J.A.; Halac, E.; Bosaleh, A.; Garcia de Davila, M.T.; Imvertasa, O.; Bramuglia, G. Frequency of CYP3A5 Genetic Polymorphisms and Tacrolimus Pharmacokinetics in Pediatric Liver Transplantation. Pharmaceutics 2020, 12, 898.

Journal reference: Pharmaceutics 2020, 12, 898
DOI: 10.3390/pharmaceutics12090898

Abstract

The body of evidence available in paediatrics population is limited for making clinical decisions regarding pharmacotherapy optimization of tacrolimus. The objective of this study was to estimate the frequency of CYP3A5 genetic polymorphisms and their relationship with tacrolimus requirements in paediatric population. This was a longitudinal cohort study, with two-year follow-up of 77 patients under 18 who had liver transplant over the period 2009-2012 at the Paediatric Hospital J. P Garrahan. Tacrolimus levels from day 5 to 2-year post-transplant were obtained from hospital records of routine therapeutic drug monitoring. The genotyping of CYP3A5 (CYP3A5*1/*3 or *3/*3) were performed in liver biopsies of both the donor and the recipient. Recipients frequency of CYP3A5 *1 expression was 37.1% and 32.2% for Donors. Patient who received an organ expresser showed lower Co/dose especially after 90 days post-surgery. The role of each polymorphism is different according to days after transplantation proceeds and it must be taken into account to optimize the benefits of TAC therapy during the post-transplant induction and maintenance phase.

Subject Areas

tacrolimus; CYP3A5; liver transplant; pharmacokinetics

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