title: Tacrolimus dosing in Chinese renal transplant recipients: a population-based pharmacogenetics study.
abstract: OBJECTIVE
  The aims of this study were to examine the effects of genetic and clinical factors on the maintenance dose of tacrolimus in patients following renal transplantation and to develop a tacrolimus-dosing model that could be combined with associated factors.
  
  
  METHODS
  This study included 142 renal transplant recipients who received tacrolimus as immunosuppressive agent. CYP3A5, MDR1 and NR1I2 gene polymorphisms were identified based on the SNaPshot assay. The relationship between the genetic and clinical factors and tacrolimus maintenance dose as well as between dose-corrected tacrolimus concentration was examined.
  
  
  RESULTS
  CYP3A5 genotype, body weight, haematocrit, haemoglobin and total bilirubin significantly influenced the maintenance tacrolimus dose. The tacrolimus-dosing model derived from linear regression model accounted for 40.5% of total variations in the tacrolimus maintenance dose.
  
  
  CONCLUSIONS
  A pharmacogenetics-based dosing model has been developed for the prediction of the tacrolimus maintenance dose in renal transplant recipients. This model may be useful in helping clinicians prescribe the initial tacrolimus dose with greater safety and effectiveness.
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, Peoples Republic of China liliang@smu.edu.cn
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Chuan-Jiang
authors.initials: CJ
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Jiang
authors.forename: Bo
authors.initials: B
authors.lastname: Si-Tu
authors.forename: Zhong-Hai
authors.initials: ZH
authors.lastname: Li
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D002681:China; D015331:Cohort Studies; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D016903:Drug Monitoring / Q000379:methods; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006239:Haplotypes; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D008954:Models, Biological; D020641:Polymorphism, Single Nucleotide; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics*; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; C000625852:NR1I2 protein, human; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus