Individualization of tacrolimus dosage based on CYP3A5 * 3 gene polymorphism: a prospective,controlled study / 中华器官移植杂志

ABSTRACT

Objective To investigate the value of Cytochrome P450 (CYP3A5) * 3 gene polymorphism in providing individualized administration for the use of tacrolimus (Tac) in renal transplantation recipients.Method Pyrophosphate sequencing method was used to determine the CYP3A5 * 3 genotype of renal transplant patients in the first day after surgery.Sixty recipients were divided into experiment group and control group.Both groups of patients were routinely given the initial dose of Tac-4.0 mg/day in the first day after surgery.The experiment group of patients were given different doses of Tac based on the different CYP3A5 * 3 genotypes at the third day after surgery [for AA0.12 mg/(kg· day),and for GG0.06 mg/(kg· day)],and the control group of patients were given different dosages of Tac according to drug concentration.Different parameters were compared between two groups of patientspercentage of patients reaching the target concentration (3-8 μg/L) at the fifth day after surgery,days required to reach the target concentration level,times needed to adjust the dosage of Tac within two weeks.Result The percentage of patients reaching the target concentration in experiment group and control group was 90％ and 46.67％,respectively (P＜ 0.05).Days required to reach the target concentration were (3.67 ± 1.32) and (7.57 ± 3.42) on average,respectively (P ＜ 0.05).Times of adjusting the Tac dose in experiment group was significantly less than those in the control group (P＜0.05).In the experiment group,the target concentration was obtained even without dosage adjustment (70％).Conclusion Individualized adjustment of Tac doses for patients according to recipients' different CYP3A5 * 3 genotypes is beneficial for reaching target concentration as soon as possible,which is superior to traditional dosage regimen.