Department of Anesthesiology and Intensive Care, Charité University Hospital Berlin-Campus Benjamin Franklin, Hindenburgdamm, Berlin, Germany.
J Clin Pharmacol. 2012 Aug;52(8):1265-72. doi: 10.1177/0091270011412968. Epub 2011 Sep 8.
In 2 crossover studies, 12 healthy volunteers (6 male/6 female) received a single oral dose of mycophenolate mofetil (MMF) 1000 mg or an equimolar dose of enteric-coated mycophenolate sodium (EC-MPS) 720 mg fasting with and without coadministered omeprazole 20 mg bid. The plasma concentrations of mycophenolic acid (MPA) and of the inactive metabolite mycophenolic acid glucuronide (MPA-G) were measured by high-performance liquid chromatography (HPLC). In addition, dissolution of MMF 500 mg or EC-MPS 360 mg tablets was determined using an USP paddle apparatus in aqueous buffer of pH 1 to 7. The bioavailability of MPA following administration of MMF or EC-MPS was similar except for the time to peak concentration, which was longer in the EC-MPS group. Concomitant treatment with omeprazole lowered significantly C(max) and AUC(12h) of MPA following administration of MMF. The pharmacokinetics of EC-MPS was not affected. Dissolution of MMF in aqueous buffer decreased dramatically at pH above 4.5. The EC-MPS tablet was stable up to pH 5. Above, EC-MPS was quantitatively disintegrated and MPS quantitatively dissolved. There is strong evidence that impaired absorption of MMF with concomitant proton pump inhibitors is due to incomplete dissolution of MMF in the stomach at elevated pH.
在 2 项交叉研究中，12 名健康志愿者（6 男/6 女）空腹单次口服霉酚酸酯（MMF）1000mg 或等量的吗替麦考酚酯钠肠溶片（EC-MPS）720mg，并同时给予奥美拉唑 20mg bid。采用高效液相色谱法（HPLC）测定霉酚酸（MPA）和无活性代谢物霉酚酸葡萄糖醛酸（MPA-G）的血浆浓度。此外，采用 USP 桨法在 pH 值为 1 至 7 的水性缓冲液中测定 MMF 500mg 或 EC-MPS 360mg 片剂的溶出度。除达峰时间（EC-MPS 组较长）外，MMF 和 EC-MPS 给药后 MPA 的生物利用度相似。奥美拉唑的伴随治疗显著降低了 MMF 给药后 MPA 的 Cmax 和 AUC（12h）。EC-MPS 的药代动力学不受影响。MMF 在水性缓冲液中的溶出度在 pH 值高于 4.5 时急剧下降。EC-MPS 片剂在 pH 值 5 以下稳定，在 pH 值高于 5 时，EC-MPS 定量崩解，MPS 定量溶解。有充分证据表明，质子泵抑制剂伴随使用时 MMF 吸收受损是由于 MMF 在胃中升高的 pH 值下不完全溶解所致。
