Eskens F A, Levitt N C, Sparreboom A, Choi L, Mather R, Verweij J, Harris A L
Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek), The Netherlands.
Clin Cancer Res. 2000 Feb;6(2):431-3.
MMI270B is a matrix metalloproteinase inhibitor (MMPI) with in vitro and in vivo activity. To exert optimal target inhibition, MMPI must be given chronically, and therefore, oral bioavailability is important. We analyzed the effect of food intake on AUC0-8 h, Cmax, and Tmax. Seventeen patients were entered into the study. Doses of MMI270B were 150, 400, and 600 mg. The first day, patients ingested the drug in a fasted state and were not allowed to eat for 2 h. The second day, patients ingested the drug 30 min after a light breakfast. Mean AUC0-8 h was not significantly influenced by food intake. Plasma concentrations were well above the IC50 of several MMPs at all doses tested. Mean Cmax was significantly decreased after food intake. Mean Tmax was significantly delayed after food intake. Food intake did not result in a significant change in exposure to MMI270B (AUC0-8 h) but did result in a significant, although not clinically relevant, decrease in peak plasma levels and time to reach peak plasma levels. No specific guidelines concerning the ingestion of MMI270B in either a fed or a fasted state are recommended.
MMI270B是一种具有体外和体内活性的基质金属蛋白酶抑制剂（MMPI）。为了实现最佳的靶点抑制，MMPI必须长期给药，因此口服生物利用度很重要。我们分析了食物摄入对AUC0-8 h、Cmax和Tmax的影响。17名患者进入该研究。MMI270B的剂量分别为150、400和600 mg。第一天，患者在禁食状态下服用药物，2小时内不允许进食。第二天，患者在清淡早餐后30分钟服用药物。食物摄入对平均AUC0-8 h没有显著影响。在所有测试剂量下，血浆浓度均远高于几种基质金属蛋白酶的IC50。食物摄入后平均Cmax显著降低。食物摄入后平均Tmax显著延迟。食物摄入并未导致MMI270B的暴露量（AUC0-8 h）发生显著变化，但确实导致血浆峰值水平和达到血浆峰值水平的时间显著降低，尽管在临床上不相关。不推荐关于在进食或禁食状态下服用MMI270B的具体指南。
