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 (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 patients who did not achieve this target level. Of the single sampling points, C2 correlates best with AUC(0-4h) (r2 = 0.86); C(0) had the poorest correlation. In an international study in 21 centres examining the absorption profiling, C2 samples were the most accurate predictors of AUC(0-4h) and freedom from rejection. In liver transplant recipients receiving Neoral -based maintenance immunosuppression, adoption of Neoral C2 monitoring identifies patients who are both over- and under-dosed, which is not distinguished by C0 measurements. Further adjustment of C2 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 C0 measurement, Neoral absorption profiling, and specifically C2 measurement, is a much more sensitive approach to assessing the pharmacokinetics and predicting the clinical effect of this formulation in the individual patient, with a consequent marked reduction in the incidence of acute cellular rejection and improved long term graft function.
Levy
G A
GA
Multi-Organ Transplantation, The Toronto Hospital, Toronto, Ontario, Canada. fg12@email.msn.com
D016572:Cyclosporine / Q000008:administration & dosage; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015166:Monitoring, Immunologic / Q000379:methods*; D016377:Organ Transplantation
D007166:Immunosuppressive Agents; D016572:Cyclosporine