Prediction of tacrolimus metabolism and dosage requirements based on CYP3A4 phenotype and CYP3A5＊3 genotype in Chinese renal transplant recipients

• Published in: Acta pharmacologica Sinica Vol. 37; no. 4; pp. 555 - 560
• Main Authors: Luo, Xi, Zhu, Li-jun, Cai, Ning-fang, Zheng, Li-yun, Cheng, Ze-neng
• Format: Journal Article
• Language: English
• Published: United States 01.04.2016
• Subjects: Asian Continental Ancestry Group; Cortisone - analogs & derivatives; Cortisone - blood; Cortisone - urine; Cytochrome P-450 CYP3A - genetics; Cytochrome P-450 CYP3A - metabolism; Humans; Hydrocortisone - analogs & derivatives; Hydrocortisone - blood; Hydrocortisone - urine; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - metabolism; Kidney Transplantation; PCR-RFLP; Tacrolimus - administration & dosage; Tacrolimus - metabolism; 中国; 代谢; 基因型; 多元回归分析; 用量; 肾移植; 预测方程
• ISSN: 1671-4083; 1745-7254; 1745-7254
• DOI: 10.1038/aps.2015.163

Aim： To examine how the endogenous CYP3A4 phenotype and CYP3A5＊3 genotype of Chinese renal transplant recipients influenced the dose-corrected trough concentration （Co/D） and weight-corrected daily dose （D/W） of tacrolimus. Methods： A total of 101 medically stable kidney transplant recipients were enrolled, and their blood and urine samples were gathered. The endogenous CYP3A4 phenotype was assessed by the ratio of 6B-hydroxycortisol and 6β hydroxycortisone to cortisol and cortisone in urine. CYP3A5＊3 genotype was determined using PCR-RELP. Results： In overall renal transplant recipients, a multiple regression analysis including the endogenous CYP3A4 phenotype, CYP3A5＊3 genotype and post-operative period accounted for 60.1% of the variability in Co/D ratio; a regression equation consisting of the endogenous CYP3A4 phenotype, post-operative period, body mass index, CYP3A5＊3 genotype, gender, total bilirubin and age explained 61.0% of the variability in D/W ratio. In CYP3A5＊3/＊3 subjects, a combination of the endogenous CYP3A4 phenotype, postoperative period and age was responsible for 65.3% of the variability in Co/D ratio; a predictive equation including the endogenous CYP3A4 phenotype, post-operative period, body mass index, gender and age explained 61.2% of the variability in the D/W ratio. Base on desired target range of tacrolimus trough concentrations, individual daily dosage regimen was calculated, and all the observed daily doses were within the predicted range. Conclusion： This study provides the equations to predict tacrolimus metabolism and dosage requirements based on the endogenous CYP3A4 phenotype, CYP3A5＊3 genotype and other non-genetic variables.