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

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Luo X, Zhu LJ, Cai NF, Zheng LY, Cheng ZN

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

Acta Pharmacol Sin. 2016 Apr;37(4):555-60. doi: 10.1038/aps.2015.163. Epub 2016 Feb 29.

PubMed ID

26924289 [ View in PubMed

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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 6beta-hydroxycortisol and 6beta-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, post-operative 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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Cortisone acetate	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate Inducer	Details