Evaluation of mycophenolic acid exposure by limited sampling strategy in Chinese adult renal transplant recipients receiving mycophenolate mofeil and tacrolimus

Abstract

Objective To investigate the pharmacokinetics of mycophenolic acid (MPA) in Chinese adult renal allograft recipients,and to generate the validated model equations for estimation of the MPA area under the plasma concentration-time curve from 0 to 12 h (AUC0-12h) with a limitedsampling strategy.Methods The pharmacokinetics in 42 Chinese renal allograft recipients treated with mycophenolate mofetil in combination with tacrolimus and corticosteroids were determined. MPA concentration was assayed by high-performance liquid chromatography (HPLC) at pre-dose (G0) and at 0.5(G0.5h),1 (C1h),1.5 (C1.5h),2 (C2h),3(C3h),4 (C4h),6 (C6h),9 (C9h) and 12 (C12h) h,respectively.The modd equations were generated by multiple stepwise regression analysis for estimation of the MPA-AUC by a limited sampling strategy.Results The prediction formulas were as follows:MPA-AUC1.5 h-4h-9 h =7.297 + 2.819C1.5 h + 3.297C4 h + 4.269C9 h ( r2 =0.878) ; and MPA-AUG0.5 h-1.5 h-4 h-9 h =2.519 + 0.549G0.5 h + 1.900 C1.5 h + 3.931 C4 h + 4.037C9 h (r2 =0.928).We plotted the average of estimated AUC and full MPA-AUC0-12 h.The Bland 8 Altman analysis indicated good agreement to within 1.96SD.Mean difference of the prediction formula using the three time points of C1.5 h-C4 h-C9 h was (11.7 ± 8.32) mg·h·L-1 and 95％ confidence interval (CI) was (9.18～14.37) mg·h·L-1,p＜0.01 ; mean difference of the prediction formula using the four time points of G0.5 h-C1.5 h C4 h-C9 h was (1.65-±7.98) mg·h·L-1,and 95％ CI (-0.84～4.13) mg·h·L-1,P＜0.01.Conclusion This limited sampling strategy provides an effective approach for estimation of full MPA AUC0-12 h in Chinese adult renal allograft recipients treated with mycophenolate mofetil in combination with tacrolimus in the stable post transplant period. Key words: Kidney transplantation; Mycophenolic acid; Pharmacokinetics