Arns Wolfgang, Breuer Stephan, Choudhury Somesh, Taccard Guy, Lee James, Binder Vera, Roettele Jürgen, Schmouder Robert
Merheim Medical Center, Cologne General Hospital, Cologne, Germany.
Clin Transplant. 2005 Apr;19(2):199-206. doi: 10.1111/j.1399-0012.2004.00318.x.
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 microg h/mL for 640 mg EC-MPS, 66.5 microg h/mL for 720 mg EC-MPS, and 63.7 microg 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.
霉酚酸（MPA）是霉酚酸酯（MMF）的活性成分，在肾移植中常规用作辅助免疫抑制疗法。尽管MMF疗法非常有效，但与显著的胃肠道不良反应相关。肠溶型霉酚酸钠（EC-MPS）是一种能递送MPA的先进制剂。肠溶衣在pH>5时溶解，使MPA能在小肠中释放。一项针对24例接受基于环孢素免疫抑制的稳定白种人肾移植患者的单中心、开放标签、随机、三向交叉研究，比较了两种EC-MPS剂量（640和720毫克）与MMF（1000毫克）的相对生物利用度。与1000毫克MMF相比，两种EC-MPS剂量的MPA平均暴露量（AUC(0-无穷大)）生物等效：640毫克EC-MPS为60.7微克·小时/毫升，720毫克EC-MPS为66.5微克·小时/毫升，1000毫克MMF为63.7微克·小时/毫升。与MMF相比，两种EC-MPS剂量的中位达峰时间（t(max)）均显著延迟（分别为2.0小时对0.75小时；p<0.01），这与EC-MPS的功能性肠溶衣一致。此外，对于霉酚酸葡萄糖醛酸的AUC和C(max)，两种EC-MPS剂量均与1000毫克MMF生物等效。所有三种治疗耐受性良好。720毫克EC-MPS剂量最接近1000毫克MMF的MPA暴露量，并被选用于后续的III期研究。
