Limited Sampling Strategy for Mycophenolic Acid in Japanese Heart Transplant Recipients

Comparison of Cyclosporin and Tacrolimus Treatment

Abstract

Background The purpose of the study was to characterize the pharmacokinetics of mycophenolic acid (MPA) in Japanese heart transplant recipients and to find the time point that has the best correlation with the MPA area under the plasma concentration curve (AUC). Methods and Results Twenty-two Japanese recipients treated with mycophenolate mofetil were evaluated in the study. Approximately 9 months after transplantation, the area under the MPA serum concentration-time curve from 0 to 12 h (AUC_{0-12 h}) was evaluated. The MPA AUC_{0-12 h} h values in the cyclosporine (CsA) and tacrolimus (FK) groups ranged from 13.11 to 50.98 μg · h/ml and from 39.19 to 93.18 μg · h/ml, respectively. Fourteen models were developed and analyzed for their ability to estimate the MPA AUC_{0-12 h} based on a limited number of samples in the CsA group. Sixteen models were developed in the FK group. The best model for predicting the full MPA AUC_{0-12 h} in the CsA group was a 3-time-point model that included C_{0 h}, C_{1 h} and C_{2 h} (r², 0.96; mean prediction error, 0.15±7.85%); a 2-time-point model that included C_{0 h}, and C_{2 h} (r², 0.94; mean prediction error, 0.495±10.35%) was also reliable. In the FK group, a 3-time-point model that included C_{1 h}, C_{2 h} and C_4h (r², 0.73; mean prediction error, 2.73±17.09%) was the best model for predicting the full MPA AUC_{0-12 h}, but it was not reliable in clinical practice. Conclusion A 3-(C_{0 h}, C_{1 h} and C_{2 h}) and a 2-time-point model (C_{0 h} and C_{2 h}) are useful for predicting the full MPA AUC_{0-12 h} in Japanese heart transplant recipients treated with CsA but not with FK. (Circ J 2007; 71: 1022 - 1028)