A PREDICTIVE MODEL FOR AREA UNDER THE CONCENTRATION VERSUS TIME CURVEOF CYCLOSPORINE-A USING SEVERAL ROUTINE MONITORING RESULTS IN RENAL-TRANSPLANT PATIENTS

We treated a predictive model for the area under the concentration ver sus time curve (AUC) of cyclosporin A (CsA) using routine monitoring r esults, and examined its clinical utility. Based on 48 clinical time c ourses accumulated from renal transplant patients, the AUC predictive model was created. An estimate of the AUC(0-8) (integrated from time z ero to 8 h) was then given as follows: )=5673.1xlog(TL)+9342.8xlog(OB) +64.1xD(prd)x869.4x 9xHCT-161.2xSCr-11.3xGPT+3.0xPL-588.6xSEX-24794.5. In this model, the AUC(0-8)(ng.h/ml) is given as a function of the Cs A trough levels (TL, ng/ml), obesity (OB, %), daily dose of prednisolo ne (D-prd, mg/d), donor type of kidney (DTK), hematocrit (HCT, %), ser um creatinine (SCr, mg/dl), glutamate-pyruvate transaminase activity ( GPT, IU/I), plasma lipids (PL, mg/dl) and sex distinction (SEX). The S tatistical significance of this multiple regression was p<0.00001 (R-2 =0.862, n=48), and the day after transplantation, neither the administ ered oral dose of CsA, or the patient's age had any contribution to th e regression. The predictive performance of this model was almost equa l to that of the existing method which used 3-point data on the concen tration versus time curve. In clinical adaptation for renal transplant patients, the steady-state concentration of CsA (C-ss) based on the A UC(0-8) predictive model was significantly decreased during acute gast roenteritis or before acute rejection, whereas nephrotoxicity was incr eased, even though CsA trough levels were within a normal therapeutic range (100-200 ng/ml). These findings suggest that the treated AUC(0-8 ) predictive model using routine monitoring results, i.e., the trough level of CsA, biochemical tests, a daily dose of predorinsolone (PRD), and basic patient information, is convenient as a monitoring device f or CsA therapy, and is satisfactory in clinical practice.