C2 Monitoring Strategy for Optimising Cyclosporin Immunosuppression from the Neoral® Formulation

Profiling of absorption of cyclosporin microemulsion (Neoral®) is a concept in therapeutic drug monitoring (TDM) designed to further optimise the clinical benefits of this formulation in transplant recipients. A single blood concentration measurement 2 hours after Neoral® administration (C2) has been shown in both liver and kidney transplant recipients to be a significantly more accurate predictor of drug exposure than trough concentrations (C0), and its use results in a reduction in the incidence and severity of cellular rejection. In a prospective trial in de novo renal transplant recipients, patients who achieved target concentrations for area under the concentration-time curve over the first 4 hours postdose (AUC0−4h) 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 patients who did not achieve this target level. Of the single sampling points, C2 correlates best with AUC0-4h(r2 = 0.86); C0 had the poorest correlation. In an international study in 21 centres examining the absorption profiling, C2 samples were the most accurate predictors of AUC0–4h and freedom from rejection.