title: A non-invasive CYP3A4 biomarker and body mass index predict cyclosporine dosage requirements in Chinese renal transplant recipients.
abstract: An endogenous CYP3A4 biomarker for in vivo metabolism of cyclosporine should be useful for optimizing individual dosage. We aimed to investigate if the combined ratio of endogenous 6β-hydroxycortisol and 6β-hydroxycortisone to cortisol and cortisone (HOM) in urine could be used as an endogenous probe for the prediction of cyclosporine dosage requirements in renal transplant recipients. 54 medically stable kidney transplant recipients participated in this study. Morning spot blood and urine samples were gathered. The multiple regression analysis including urinary HOM and body mass index accounted for 73.1% of variability in blood concentration/dose ratio (C/D) of cyclosporine, in which urinary HOM and body mass index contributed 64.9% and 8.2%, respectively. Based on the present approach, individual dosage regimen of CsA could be acquired without therapeutic drug monitoring and the results showed that all of the observed stable doses of CsA were within the predicted range during different post-operative periods. In summary, there is a significant relationship between endogenous CYP3A4 biomarker (assessed by urinary HOM) and in vivo metabolism of cyclosporine in renal transplant recipients. Urinary HOM and body mass index are important predictors of cyclosporine metabolism. Our findings provide clinical implications that the predictive algorithm based on a simple, safe and non-invasive CYP3A4 phenotyping can be anticipated.
authors.forename: Ningfang
authors.initials: N
authors.lastname: Cai
authors.forename: Bifeng
authors.initials: B
authors.lastname: Li
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Huang
authors.forename: Kezhen
authors.initials: K
authors.lastname: Xu
authors.forename: Huiping
authors.initials: H
authors.lastname: Feng
authors.forename: Zeneng
authors.initials: Z
authors.lastname: Cheng
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhu
authors.forename: Liyun
authors.initials: L
authors.lastname: Zheng
authors.forename: Xi
authors.initials: X
authors.lastname: Luo
mesh_terms: D000328:Adult; D044466:Asian People; D015415:Biomarkers / Q000032:analysis*; D015992:Body Mass Index; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A / Q000032:analysis*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; C001380:6 beta-hydroxycortisol; D016572:Cyclosporine; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D006854:Hydrocortisone