细胞色素P450 3A5基因多态性对肾移植受者他克莫司剂量及浓度-剂量比的影响

Impact of cytochrome p450 3A5 genetic polymorphism on tacrolimus doses and concentration-to-dose ratio in renal transplant recipients.

作者信息

Thervet Eric, Anglicheau Dany, King Barry, Schlageter Marie-Hélène, Cassinat Bruno, Beaune Philippe, Legendre Christophe, Daly Ann K

机构信息

INSERM UMR S490, Centre Universitaire des Saints-Pères, Paris, France.

出版信息

Transplantation. 2003 Oct 27;76(8):1233-5. doi: 10.1097/01.TP.0000090753.99170.89.

DOI:10.1097/01.TP.0000090753.99170.89

PMID:14578760

Abstract

BACKGROUND

Tacrolimus pharmacokinetic characteristics vary greatly among individuals. Tacrolimus is a substrate of cytochrome p450 (CYP), of subfamily CYP3A. CYP3A activity is the sum of the activities of the family of CYP3A genes, including CYP3A5. Subjects with the CYP3A5*1/1 genotype express large amounts of CYP3A5. Heterozygotes (genotype CYP3A51/*3) also express the enzyme. We postulated that CYP3A5 polymorphism is associated with tacrolimus pharmacokinetic variations.

METHODS

CYP3A5 genotype was evaluated in 80 renal transplant recipients and correlated with the daily tacrolimus dose and concentration-to-dose ratio.

RESULTS

The frequency of the homozygous CYP3A51 genotype (CYP3A51/1) was 5%, and 11% of subjects were heterozygous (CYP3A51/3). The mean doses required to obtain the targeted concentration-to-dose ratio were significantly lower in patients with the CYP3A51/*1 genotype.

CONCLUSIONS

Determination of CYP3A5 genotype is predictive of the dose of tacrolimus in renal transplant recipients and may help to determine the initial daily dose needed by individual patients for adequate immunosuppression without excess nephrotoxicity.

摘要

背景

他克莫司的药代动力学特征在个体间差异很大。他克莫司是细胞色素P450（CYP）亚家族CYP3A的底物。CYP3A活性是包括CYP3A5在内的CYP3A基因家族活性的总和。具有CYP3A5*1/1基因型的受试者表达大量的CYP3A5。杂合子（基因型CYP3A51/*3）也表达该酶。我们推测CYP3A5基因多态性与他克莫司的药代动力学变异有关。