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  • Title: 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.
    Author: Cai W, Cai Q, Xiong N, Qin Y, Lai L, Sun X, Hu Y.
    Journal: Transplant Proc; 2018 Jun; 50(5):1298-1304. PubMed ID: 29735215.
    Abstract:
    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 (AUC0-12h) 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 (Cmax) 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-AUCMMFdt = 3.542 + 3.332C0.5h + 1.117C1.5h + 3.946C4h (adjusted r2 = 0.90, P < .001); MPA-AUCMMFc = 8.149 + 1.442C2h + 1.056C4h + 7.133C6h (adjusted r2 = 0.88, P < .001). Both predicted and measured AUCs showed good consistency. CONCLUSIONS: After treatment with MMF dispersible tables or MMF capsules, the Cmax 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 AUC0-12h of MPA.
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