Limited Sampling Strategy for Estimating Mycophenolic Acid Exposure on Day 7 Post-Transplant for Two Mycophenolate Mofetil Formulations Derived From 20 Chinese Renal Transplant Recipients

Purpose. To assess the pharmacokinetic properties of mycophenolate mofetil (MMF) dispersible tablets and capsules by the enzyme multiplied immunoassay technique (EMIT) in Chinese kidney transplant recipients in the early post-transplantation phase and to develop the equations to predict mycophenolic acid (MPA) area under the 12-hour concentration-time curve (AUC(0-12h )) using a limited sampling strategy (LSS). Methods. Forty patients who underwent renal transplantation from brain-dead donors were randomly divided into dispersible tablets (Sai KE Ping; Hangzhou Zhongmei Huadong Pharma) and capsules (Cellcept; Roche Pharma, Why, NSW, Australia) groups, and treated with MMF combined with combination tacrolimus and prednisone as a basic immunosuppressive regimen. Blood samples were collected before treatment (0) and at 0.5,1, 1.5, 2, 4, 6, 8, 10, and 12 hours post-treatment and 7 days after renal transplantation. Plasma MPA concentrations were measured using EMIT. LSS equations were identified using multiple stepwise linear regression analysis. Results. The peak concentration (C-max) in the MMF dispersible tablets (MMFdt) group (7.0 +/- 2.8) mg/L was reduced compared with that in the MMF capsules (MMFc) group (10.8 +/- 6.2 mg/L; P = .012); time to peak concentration in the MMFdt group was 3.2 +/- 2.3 hours, which was nonsignificantly elevated compared with that of the MMFc group (2.2 + 1.7 hours). Three-point estimation formulas were generated by multiple linear regression for both groups: MPA-AUC(MMFdt) = 3.542 + 3.332C(0.5h) + 1.117C(1.5h) + 3.946C(4h) (adjusted r(2) = 0.90, P < .001); MPA-AUC(MMFc) = 8.149 + 1.442C(2h) + 1.056C(4h) + 7.133C(6h) (adjusted r(2) = 0.88, P < .001). Both predicted and measured AUCs showed good consistency. Conclusions. After treatment with MMF dispersible tables or MMF capsules, the C max of MPA for the MMFdt group was significantly lower than that of the MMFc group; there was no significant difference in other pharmacokinetic parameters. Three-time point equations can be used as a predictable measure of the AUC(0-12h) of MPA.