RESUMO
Objective:To explore the effect of MDR1(C3435T) gene polymorphism on tacrolimus metabolism early after pediatric liver transplantation.Methods:Preoperative blood samples of 90 donors and recipients of pediatric liver transplantation were collected and genotyped. According to the CYP3A5 genotype of donor/recipient, they were divided into four subgroups of recipient slow metabolism/donor slow metabolism (R/D-S), recipient fast metabolism/donor slow metabolism (R-F/D-S), recipient slow metabolism/donor fast metabolism (R-S/D-F) and recipient fast metabolism/donor fast metabolism (R/D-F). The values of concentration/daily dose (C 0/D) of tacrolimus in patients with different MDR1 genotypes were compared at the subgroup level. Results:The C 0/D value of MDR1 TT recipients was significantly higher than that of CC/ CT counterparts in the first week after liver transplantation ( P<0.01). The C 0/D value of CT recipients in R/D-S subgroup was significantly higher than that of CC counterparts in the 2nd week after operation ( P<0.05). The C 0/D value of CT recipients in R/D-F subgroup was significantly higher than that of CC counterparts in 2 weeks ( P<0.05) and 3 weeks ( P<0.01). Conclusions:MDR1(C3435T) gene polymorphism in recipients affects tacrolimus metabolism. Recipients with CC genotype metabolize faster than those with CT/TT genotypes. And the same daily dose and tacrolimus blood concentration are lower. Recipients with different MDR1 genotypes need to adjust the dosage of tacrolimus. This difference is more obvious in CYP3A5 fast metabolic subgroup, more attention should be paid to optimizing individualizing dosage regimens, reducing the incidence of adverse reactions and improving the efficacy.
RESUMO
Objective To explore the influencing factors of blood concentration of tacrolimus in pediatric living donor liver transplant recipients and provide rationales for individualized administration of tacrolimus .Methods Trough concentrations (C0 ) , doses of tacrolimus , recipient age , gender , body weight ,donor and recipient CYP3A5 genotypes ,hematocrit (HCT ) and liver/kidney function related indicators at 3 ,5 ,7 ,14 days ,1 month , 2 months and 3 months post living donor liver transplantation were collected from a total of 100 pediatric recipients .Taking ratio of concentration to dose (C0 /D) as a dependent variable ,the influencing factors of blood concentration of tacrolimus were analyzed by multivariate stepwise regression .Results The influencing factors of blood tacrolimus concentration at 3d post-transplantation were recipient CYP3A5 genotyp , donor CYP3A5 genotype and weight of recipients . The major influencing factors at 5d post-transplantation were recipient & donor CYP3A5 genotypes , recipient weight and HCT . The major relevant factors at 7d posttransplantation were CYP3A5 of recipients ,age and HCT .The influencing factors at 14 days were the same as those at 2 months ,i .e .CYP3A5 genotype and weight of recipients .At 1 month the major influencing factors were weight of recipients ,CYP3A5 of recipients and alkaline phosphatase (ALP) ; CYP3A5 genotype and weight of recipients at 3 months . Further study on CYP3A5 genotype of donors and recipients , the C0 /D ratio of CYP3A5 genotype non-expression group was significantly higher than that of expression group in recipients and C0 /D ratio of donor CYP3A5 genotype nonexpression group was significantly higher than that of expression group .Conclusions The influencing factors of concentration of tacrolimusvary at different timepoints after liver transplantation . Paying close attention to the changes of CYP3A5 genotype , weight of recipients and related biochemical indexes and considering various influencing factors facilitate individualized dosing for improving the prognosis of pediatric recipients .