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

Pharmaceutics

JeffersonAntonio Buendía¹  Guillermo Bramuglia²  Oscar Imvertasa³  Esteban Halac³  Andrea Bosaleh⁴  MaríaT. Garcia de Davila⁴ 

[1] Department of Pharmacology and Toxicology, Faculty of Medicine, University of Antioquia, Medellin 050010, Colombia;Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires C1113, Argentina;Liver Transplant Service, J.P. Garrahan Hospital, Buenos Aires C1245AAM, Argentina;Pathology Service, J.P. Garrahan Hospital, Buenos Aires C1245AAM, Argentina;

关键词: tacrolimus;    CYP3A5;    liver transplant;    pharmacokinetics;   

DOI  :  10.3390/pharmaceutics12090898

来源: DOAJ

【 摘 要 】

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

【 授权许可】

Unknown