title: Dose adjustment strategy of cyclosporine A in renal transplant patients: evaluation of anthropometric parameters for dose adjustment and C0 vs. C2 monitoring in Japan, 2001-2010.
abstract: The optimal use and monitoring of cyclosporine A (CyA) have remained unclear and the current strategy of CyA treatment requires frequent dose adjustment following an empirical initial dosage adjusted for total body weight (TBW). The primary aim of this study was to evaluate age and anthropometric parameters as predictors for dose adjustment of CyA; and the secondary aim was to compare the usefulness of the concentration at predose (C0) and 2-hour postdose (C2) monitoring. An open-label, non-randomized, retrospective study was performed in 81 renal transplant patients in Japan during 2001-2010. The relationships between the area under the blood concentration-time curve (AUC0-9) of CyA and its C0 or C2 level were assessed with a linear regression analysis model. In addition to age, 7 anthropometric parameters were tested as predictors for AUC0-9 of CyA: TBW, height (HT), body mass index (BMI), body surface area (BSA), ideal body weight (IBW), lean body weight (LBW), and fat free mass (FFM). Correlations between AUC0-9 of CyA and these parameters were also analyzed with a linear regression model. The rank order of the correlation coefficient was C0 > C2 (C0; r=0.6273, C2; r=0.5562). The linear regression analyses between AUC0-9 of CyA and candidate parameters indicated their potential usefulness from the following rank order: IBW > FFM > HT > BSA > LBW > TBW > BMI > Age. In conclusion, after oral administration, C2 monitoring has a large variation and could be at high risk for overdosing. Therefore, after oral dosing of CyA, it was not considered to be a useful approach for single monitoring, but should rather be used with C0 monitoring. The regression analyses between AUC0-9 of CyA and anthropometric parameters indicated that IBW was potentially the superior predictor for dose adjustment of CyA in an empiric strategy using TBW (IBW; r=0.5181, TBW; r=0.3192); however, this finding seems to lack the pharmacokinetic rationale and thus warrants further basic and clinical investigations.
authors.affiliation: 1. Department of Hospital Pharmacy, Kyoto Prefectural University of Medicine.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Kokuhu
authors.forename: Keizo
authors.initials: K
authors.lastname: Fukushima
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Ushigome
authors.forename: Norio
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sugioka
mesh_terms: D000328:Adult; D000886:Anthropometry / Q000379:methods*; D019540:Area Under Curve; D016572:Cyclosporine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D007564:Japan; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine
keywords: C0 monitoring; C2 monitoring; cyclosporine; dose adjustment; ideal body weight