Pharmacokinetics of enteric-coated mycophenolate sodium in Chinese adult renal allograft recipients with steroids withdrawal

Objective To investigate the pharmacokinetics of enteric-coated mycophenolate sodium in Chinese adult renal allograft recipients with steroids withdrawal and to generate the optimal model equations for estimation of the MPA area under the plasma concentration-time curve from 0 to 12 hours (AUC0-12 h) with a limited sampling strategy. Methods The pharmacokinetics in 30 Chinese renal allograft recipients treated with EC-MPS in combination with tacrolimus in the stable post-transplant period were determined. MPA concentration was assayed by high performance liquid chromatography (HPLC) at pre-dose (C0) and 1(C1), 2.5 (C2.5), 4 (C4), 5(C5), 6 (C6), 7(C7), 8(C8) , 9(C9), 10.5(C10.5) and 12 (C12) hours after the morning dose of EC-MPS following an overnight fast. The model equations were generated by multiple stepwise regression analysis for estimation of the MPA-AUC. Results The best predictive equation model of systemic drug exposure was the following: MPA-AUC2.5 h-4 h-7 h-12 h=15.889+ 0.692·C2.5+ 1.071·C4+ 4.948·C7+ 4.477·C12 (r2=0.878). The equation model showed an optimal agreement between the full AUCs and estimated AUCs by using Bland and Altman analysis. The mean absolute prediction error(APE%) for equation were 11.8%±10.2%. Conclusions Limited sampling strategies are useful for MPA-AUC0-12 h monitoring in renal transplant recipients receiving EC-MPS. This predictive equation model provides an effective approach for estimation of full MPA-AUC0-12 h in Chinese adult renal allograft recipients treated with EC-MPS in combination with tacrolimus with steroids withdrawal. Key words: Kidney Transplantation; Hormones; Pharmacokinetics