Influence of cyclosporine pharmacokinetics, trough concentrations, and AUC monitoring on outcome after kidney transplantation

Abstract

To assess the importance of cyclosporine pharmacokinetics on graft outcome and acute rejection episodes, pretransplant and a total of 1868 posttransplant whole-blood cyclosporine pharmacokinetic profiles were performed in 160 consecutive kidney transplant recipients. The following posttransplant pharmacokinetic risk factors were associated with a poorer graft survival and a higher incidence of acute rejection: F, < 25%; clearance, > 325 ml/min; steady-state cyclosporine concentrations, < 350 ng/ml during intravenous infusion; or average cyclosporine concentrations, < 400 ng/ml during the first oral study. Although the discrimination between rejecting and nonrejecting patients was greatest for cyclosporine concentrations obtained at 24 hours after drug administration, measurements at 6 and 14 hours, as well as average concentrations, were all highly predictive. Because of the strong association between the cyclosporine concentrations and outcome, an equation is described to provide initial oral dose prediction. Furthermore, this association suggests that improved cyclosporine pharmacokinetic monitoring may aid in improving outcome after kidney transplantation.