title: Prediction of tacrolimus metabolism and dosage requirements based on CYP3A4 phenotype and CYP3A5(*)3 genotype in Chinese renal transplant recipients.
abstract: OBJECTIVE
  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, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Life Sciences, Central South University, Changsha 410083, China.|School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.|The State Key Laboratory of Medical Genetics, Central South University, Changsha 410078, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Luo
authors.affiliation: Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, the 3rd Affiliated Hospital of Xiangya Medical Institute, Central South University, Changsha 410013, China.
authors.forename: Li-jun
authors.initials: LJ
authors.lastname: Zhu
authors.affiliation: Department of Pharmacy, Zhangzhou Municipal Hospital of Fujian Province, Zhangzhou 363000, China.
authors.forename: Ning-fang
authors.initials: NF
authors.lastname: Cai
authors.affiliation: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors.forename: Li-yun
authors.initials: LY
authors.lastname: Zheng
authors.affiliation: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors.forename: Ze-neng
authors.initials: ZN
authors.lastname: Cheng
mesh_terms: D044466:Asian People; D003348:Cortisone / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000378:metabolism*; D016030:Kidney Transplantation; D016559:Tacrolimus / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: C485511:6 beta-hydroxycortisone; D007166:Immunosuppressive Agents; C001380:6 beta-hydroxycortisol; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D003348:Cortisone; D006854:Hydrocortisone; D016559:Tacrolimus