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

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 (C(0)) and 2-hour postdose (C(2)) 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 (AUC(0-9)) of CyA and its C(0) or C(2) level were assessed with a linear regression analysis model. In addition to age, 7 anthropometric parameters were tested as predictors for AUC(0-9) 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 AUC(0-9) of CyA and these parameters were also analyzed with a linear regression model. The rank order of the correlation coefficient was C(0) > C(2) (C(0); r=0.6273, C(2); r=0.5562). The linear regression analyses between AUC(0-9) 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, C(2) 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 C(0) monitoring. The regression analyses between AUC(0-9) 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.