Desarrollo de modelos farmacocinéticos de Tacrolimus en distintas poblaciones de pacientes trasplantados hepáticos: caracterización de variables clínicas y genéticas asociadas a la variabilidad farmacocinética/farmacodinámica

摘要

Background: Relative influence of donor and recipient CYP3A5*3 variant genotype in PK- Tacrolimus (TAC) of liver transplant recipients is inconclusive. The objective of this study was to investigate the influence of CYP3A5 polymorphism of recipients as well as donors on the (TAC) pharmacokinetics in Argentinean population.Methods: We evaluated the influence of CYP3A5 polymorphism of recipients as well as donors on the Tacrolimus (TAC) pharmacokinetics in 24 stable liver transplant patient and 77 pediatric patients for two years of follow-up Results: The percentage of CYP3A5 expressers (*1/*1 and *1/*3 genotypes) were between 17% and 37%. Recipient expression of a CYP3A5*1 allele seemed to have the greatest influence on Co/dose ratio of TAC in the immediate posttransplant period and the donors? hepatic genotype in increasing role with time.Conclusions: In the immediate posttransplant period, recipient expression of a CYP3A5*1 allele seemed to have the greatest influence on TAC pharmacokinetics with donor expression of a CYP3A5*1 allelle possibly becoming more important with increasing time after transplant.