Pharmacokinetic Study and Limited Sampling Strategy of Cyclosporine in Japanese Heart Transplant Recipients

Abstract

The purpose of this study was to characterize the pharmacokinetics of cyclosporine (CsA) in Japanese heart transplant patients, and to optimise the monitoring strategy based on measurements of the area under the curve of plasma concentration absorption phase or 2 h post-dose concentrations (C(2)). At defined time periods during the first year after transplantation, the area under the curve for the CsA serum concentration from 0 to 4 h (AUC(0-4 h)) was evaluated. Pharmacokinetic parameters and renal function at 1 month and 12 months after transplantation were compared in 7 Japanese patients. The highest coefficient of determination between CsA AUC(0-4 h) and a single concentration was observed using C2 (r2 =0.838). For CsA pharmacokinetics, the mean measurement of whole blood trough levels value at 12 months was significantly lower than at 1 month after transplantation (p=0.026). The mean serum creatinine level at 12 months was significantly higher than at 1 month (1.00 mg/dl vs 0.73 p=0.0194). A single-time-point model that includes C2 is useful for predicting CsA AUC(0-4 h) in Japanese heart transplant patients. Mean C2 values >1,000 ng/ml were obtained in patients with no rejection at 1 month and 12 months after transplantation; however, renal impairment may occur.