The influence of tacrolimus concentration/dose ratio and curative effect in early postoperative period of children living donor liver transplantation based on the CYP3A5 genotype

Abstract

Objective To investigate the relationship between CYP3A5 gene polymorphism and tacrolimus concentration/dose ratio in children living donor liver transplantation and the correlation with clinical efficacy, for the relatives living donor liver transplantation in children tacrolimus individualized medication providing reference indicators. Methods Peripheral blood samples were collected from children with relatives living donor liver transplantation in the center of liver transplantation, the genotype of CYP3A5 was determined by polymerase chain reaction (PCR)/pyrophosphate sequencing, The dosage of tacrolimus and blood concentration, liver and kidney function and other related indicators were measured within 3 months after operation. According to genotypes, the children can be divided into gene expression group (CYP3A5*1/*1 and CYP3A5*1/*3) and non - expression group (CYP3A5*3/*3). The drug concentration (C0), tacrolimus dose / body weight (D/W) ratio , drug concentration/dose (C0/D) ratio of each genotype at 1 day, 3 d, 5 d, 7 d, 14 d, 28 d, 2 months and 3 months after administration and the genotype at the time point on liver and kidney function was carried out statistics. Results Among the 80 cases, 36 cases (45.0%) were CYP3A5*3/*3, 37 cases (46.2%) were CYP3A5*1/*3, 7 cases (8.8%) were CYP3A5*1/*1. CYP3A5 gene expression group reached a therapeutic concentration range (C0> 8 μg/L) than the gene non-expression group takes longer time. There was no significant difference in CYP3A5 gene expression group between the non-expression group on the initial dose (P>0.05); CYP3A5 gene expression group than the non-expression group, tacrolimus C0 within 1 month after operation were statistically significant.CYP3A5 gene expression group than the non-expression group, tacrolimus D/W in addition to the first day after surgery, other time points were statistically significant (P 0.05), but there was significant difference in the alkaline phosphatase. Conclusion CYP3A5 gene expression in children than non-expression group of children need higher doses to reach the therapeutic drug concentration; CYP3A5 gene polymorphism had significant effects on early tacrolimus C0, D/W and C0/D values; CYP3A5 gene polymorphism is instructive for the administration of tacrolimus in children with living donor liver transplantation, CYP3A5 gene type tests should be regular, improve efficacy and reduce the incidence of adverse reactions. Key words: children living donor liver transplantation; Cytochrome P-450; Tacrolimus; drug concentration