A simple method to calculate cyclosporine dosage to obtain a target C2 drug level

C(2) Cyclosporine (CsA) level, as a surrogate of area under the time-concentration curve (AUC) 0-4 hours, is a good predictor of drug absorption and clinical outcome after kidney transplantation. It has been difficult to define the optimal C(2) level in the individual case and given the broad range of C(2) due to interindividual absorption variability it has been troublesome to determine the drug dose needed to obtain an expected C(2)-CsA concentration. In this study data of 16 stable renal and renal/pancreas recipients treated with prednisone, azathioprine, and CsA (Neoral) managed by C(0) level was examined. CsA concentrations at time 0 (basal), 2, 6, and 12 hours post CsA (Neoral) intake were determined the day of the study. A significant linear regression level was established between C(2) (but not C(0), C(6) and C(12)) and the dosage expressed as mg/kg/d (P = 0.0113, correlation coefficient r = 0.573018). Subsequently, another 27 renal transplant recipients were studied retrospectively and divided into three groups according to posttransplant period: 1 to 6, 7 to 12, and beyond 12 months after transplant. Equations derived from the relationship between C(2) and dose (mg/kg/d) were similar between the three groups and when compared with the first study. A formula obtained from the 27 patients in the whole posttransplant period (mg/kg/d = C(2) x 0.0010208 + 1.86125) was applied to patients of the first study obtaining a regression coefficient between actual and calculated CsA dose of 0.6145 (P = 0.01). A more accurate equation (P = 0.0001, r = 0.5925) was obtained by analyzing 145 C(2) determinations covering a period from 1 month to 8 years following transplant which gave a linear regression line defined by the equation C(2) x 0.001473 + 1.6673. This equation would permit the calculation mg/kg/d of CsA (Neoral) dose to obtain an expected C(2) level. The derived equation shown in this paper has a predictive value of 50% to 60% only, but can help to find adequate dosage in the presence of an inappropriate C(2) level.