Enteric-coated mycophenolate sodium delivers bioequivalent MPA exposure compared with mycophenolate mofetil
Enteric-coated mycophenolate sodium delivers bioequivalent MPA exposure compared with mycophenolate mofetil
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DOI：
10.1111/j.1399-0012.2004.00318.x
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发表时间：
2005-04-01
影响因子：
2.1
通讯作者：
Schmouder, R
中科院分区：
文献类型：
--
作者：
Arns, W;Breuer, S;Schmouder, R
霉酚酸（MPA）是霉酚酸酯（MMF）的活性成分，常用于肾移植的辅助免疫抑制治疗。虽然非常有效，但MMF治疗与显著的胃肠道不良反应相关。麦考酚钠肠溶衣（EC-MPS）是一种新型的MPA给药制剂。肠溶衣在pH > 5时溶解，允许MPA在小肠中递送。一项在24例接受基于环孢菌素的免疫抑制的稳定白人肾移植患者中进行的单中心、开放标签、随机、三向交叉研究，比较了两种EC-MPS剂量（640和720 mg）与MMF（1000 mg）的相对生物利用度。与1000 mg MMF相比，两种EC-MPS剂量的平均MPA暴露量（AUC（0-无穷大））具有生物等效性：640 mg EC-MPS为60.7 mug h/mL，720 mg EC-MPS为66.5 mug h/mL，1000 mg MMF为63.7 mug h/mL。与MMF相比，两种EC-MPS剂量的中位t（max）显著延迟（分别为2.0 h vs. 0.75 h; p < 0.01），与EC-MPS的功能性肠溶包衣一致。此外，对于麦考酚酸葡糖苷酸的AUC和C-max，两种EC-MPS剂量与1000 mg MMF具有生物等效性。所有三种治疗均耐受良好。EC-MPS 720 mg剂量最接近MPA暴露量1000 mg MMF，并被选择用于后续III期研究。
Mycophenolic acid (MPA), the active moiety of mycophenolate mofetil (MMF), is routinely used as an adjunct immunosuppressant therapy in renal transplantation. Although highly effective, MMF therapy is associated with significant gastrointestinal adverse effects. Enteric-coated mycophenolate sodium (EC-MPS) is an advanced formulation delivering MPA. The enteric coat dissolves at pH > 5 allowing for MPA delivery in the small intestine. A single-center, open-label, randomized, three-way crossover study of 24 stable Caucasian renal transplant patients receiving cyclosporine-based immunosuppression, compared the relative bioavailability of two EC-MPS doses (640 and 720 mg) with MMF (1000 mg). Both EC-MPS doses delivered bioequivalent mean MPA exposure (AUC(0-infinity)) compared with 1000 mg MMF: 60.7 mug h/mL for 640 mg EC-MPS, 66.5 mug h/mL for 720 mg EC-MPS, and 63.7 mug h/mL for 1000 mg MMF. Median t(max) was significantly delayed for both EC-MPS doses compared with MMF (2.0 h vs. 0.75 h, respectively; p < 0.01), consistent with a functional enteric coating of EC-MPS. Furthermore, both EC-MPS doses were bioequivalent to 1000 mg MMF for AUC and C-max for mycophenolic acid glucuronide. All three treatments were well tolerated. The EC-MPS 720 mg dose most closely approximated the MPA exposure of 1000 mg MMF and was selected for subsequent phase III studies.