C-2 monitoring strategy for optimising cyclosporin immunosuppression from the neoral((R) 1) formulation

Profiling of absorption of cyclosporin microemulsion (Neoral((R))) is a con cept in therapeutic drug monitoring (TDM) designed to further optimise the clinical benefits of this formulation in transplant recipients. A single bl ood concentration measurement 2 hours after Neoral((R)) administration (Cz) has been shown in both Liver and kidney transplant recipients to be a sign ificantly more accurate predictor of drug exposure than trough concentratio ns (C-0), and its use results in a reduction in the incidence and severity of cellular rejection. In a prospective trial in de novo renal transplant r ecipients, patients who achieved target concentrations for area under the c oncentration-rime curve over the first 4 hours postdose (AUC(0-4h)) of 4500 to 5500 ng (.) h/ml within 5 days of transplantation had a 7% incidence of histological acute rejection, compared with 37% rejection in those patient s who did not achieve this target level. Of the single sampling points, C-2 correlates best with AUC(0-4h) (r(2) = 0.86); C-0 had the poorest correlat ion. In an international study in 21 centres examining the absorption profi ling, C-2 samples were the most accurate predictors of AUC(0-4h) and freedo m from rejection. In liver transplant recipients receiving Neoral((R))-based maintenance immu nosuppression, adoption of Neoral((R)) C-2 monitoring identifies patients w ho are both over- and under-dosed, which is not distinguished by C-0 measur ements. Further adjustment of C-2 to recommended targets, even at 5 and 10 years after transplantation, results in reduction in nephrotoxicity without exposing the patient to the risk of rejection. In summary, despite a level of simplicity comparable to C-0 measurement, Ne oral((R)) absorption profiling, and specifically C-2 measurement, is a much more sensitive approach to assessing the pharmacokinetics and predicting t he clinical effect of this formulation in the individual patient, with a co nsequent marked reduction in the incidence of acute cellular rejection and improved long term graft function.