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

   
@article{APS9461,
	author = {Xi LUO and Li-jun ZHU and Ning-fang CAI and Li-yun ZHENG and Ze-neng CHENG},
	title = {Prediction of tacrolimus metabolism and dosage requirements based on CYP3A4 phenotype and  CYP3A5*3  genotype in Chinese renal transplant recipients},
	journal = {Acta Pharmacologica Sinica},
	volume = {37},
	number = {4},
	year = {2017},
	keywords = {},
	abstract = {Aim:  To examine how the endogenous CYP3A4 phenotype and CYP3A5*3 genotype of Chinese renal transplant recipients influenced the dose-corrected trough concentration (C0/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 6β-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 C0/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 C0/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.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/9461}
}