Prediction of cyclosporine area under the curve using a three-point sampling strategy after Neoral administration

Abstract

Accurate monitoring of cyclosporine (CsA) dosage is still a problem, because measurement of the area under the curve (AUC)--the most appropriate indicator of exposure to CsA--requires a number of blood samples to be taken over 12 h, which makes monitoring difficult in day-to-day clinical practice. This study investigated whether a limited sampling strategy in human kidney transplantation reflected the actual AUC better in patients given Neoral than in those being treated with Sandimmune. Stepwise multiple regression analysis of CsA blood levels recorded after Neoral administration to 20 renal transplant patients showed the best results in AUC prediction with three sampling points (1.5, 8, 11 h after Neoral dosing; r = 0.992 with an associated error in AUC prediction ranging from -8.0 to 8.8%). Because blood sampling at 8 and 11 h is not feasible in routine clinical practice, sample points from 0 to 3 h after Neoral dosing, i.e., up to the time of maximum mean blood CsA concentration plus 2 SD, were considered. The best results were obtained with a three-point strategy (0, 1, and 3 h after Neoral dosing; error in prediction: -9.0 to 7.2%), which gave an excellent correlation between measured and predicted AUC (r = 0.989). A similar analysis after Sandimmune given to the same patients always resulted in poor AUC prediction with a wide associated error. These findings indicate that with Neoral, but not Sandimmune, a limited strategy of three-point sampling taken early after dosing allows an excellent and perfectly reliable prediction of the actual AUC.