RELATIONSHIP BETWEEN AREA UNDER THE CONCENTRATION VERSUS TIME CURVE OF CYCLOSPORINE-A, CREATININE CLEARANCE, HEMATOCRIT VALUE, AND OTHER CLINICAL FACTORS IN JAPANESE RENAL-TRANSPLANT PATIENTS

We evaluated the relationship between the area under the concentration versus time curve (AUG) of cyclosporin A (CsA) and several other clin ical factors, because the clinical utility of AUC monitoring has been ambiguous. Fifty-four clinical time courses from 14 Japanese renal tra nsplant patients during hospitalization, in the period from April 1990 to March 1997, were examined. In a bivariate regression analysis ther e was no correlation between the AUC and the daily dose of CsA (mg/kg/ day) when the individual data or total series data were analyzed. In a chi-square test, the donor type of kidney (chi(2) = 25.254, df = 1, p = 0.0000) and renal function-related episodes, i.e. acute tubular nec rosis, hemodialysis, hypertension, nephrotoxicity, or rejection (chi(2 ) = 13.982, df = 1, p = 0.0002) directly affected posttransplant renal function assessed by creatinine clearance, while episodes of hepatic function as assessed by the glutamate-pyruvate transaminase (GPT) acti vity level had no correlation with the posttransplant renal function e valuated according to creatinine clearance. In contrast, the renal fun ction-related episodes significantly affected the AUC after renal tran splantation (chi(2) = 4.934, df = 1, p = 0.0263), while hepatic functi on assessed by GPT did not. In a multivariate analysis, the creatinine clearance and obesity had signifcant positive correlations with the A UG, whereas the hematocrit had a significant negative correlation with the AUC. From these observations, we concluded that the dosage adjust ment of CsA cannot be performed using the linear relationship between the daily oral dose and the AUG, and that renal function, obesity, and the CsA blood distribution properties affect the CsA pharmacokinetics after renal transplantation. Posttransplant renal function as well as obesity and CsA blood distribution properties are important factors t o be considered when therapeutic monitoring is performed.