Cross Research S.A., Via F. A. Giorgioli, 14, Arzo CH-6864, Switzerland.
Cross Research S.A., Via F. A. Giorgioli, 14, Arzo CH-6864, Switzerland.
Contemp Clin Trials. 2018 Aug;71:96-102. doi: 10.1016/j.cct.2018.06.001. Epub 2018 Jun 2.
Methylene blue-MMX® tablets are proposed as an aid for detection and visualisation of adenomas and carcinomas in patients undergoing colonoscopy, by improving their detection rate and highlighting the presence of the intestinal dysplastic lesions. Single total doses of 100 and 200 mg were administered to healthy volunteers undergoing a bowel cleansing preparation and a full colonoscopy to investigate the colonic staining. The pharmacokinetics of methylene blue and the safety after exposure to the tablets were also investigated. With 200 mg, the best staining, assessed as the sum of acceptable and good staining, was achieved in the ascending colon and rectosigmoid (75% subjects each), the transverse and the descending colon (approximately 63% each). Absence of staining or overstaining were reported for no colonic region of interest in any subject. Similar results were observed in the 100 mg dose group. Methylene blue blood concentrations reached a peak (C) in a median time (T) of 12 h with 100 mg and 16 h with 200 mg. AUC was 10.7 ± 6.7 μg/mLxh after 100 mg and 25.2 ± 7.4 μg/mLxh after 200 mg. Half-life ranged between 9 and 22 h after the lower dose and between 6 and 26 h after the higher dose. The cumulative urinary excretion was about 28% after 100 mg and about 39% after 200 mg up to 60 h post-dose. The overall frequency of adverse events after single dose of the test product administered along with a bowel cleansing preparation was 39%, but only one was related to the test product: abnormal transaminases. The most frequent adverse event was a transient polyuria (17%). One serious adverse event (gastrointestinal haemorrhage) led the subject to study discontinuation and hospitalisation and another subject withdrew the study due to one adverse event (haematemesis). Either event was not related to methylene blue.
美蓝 MMX® 片剂被提议作为一种辅助手段，用于提高腺瘤和癌在接受结肠镜检查患者中的检出率，并突显肠异型性病变的存在，从而帮助检测和可视化这些病变。在接受肠道清洁准备和全结肠镜检查的健康志愿者中，给予 100 和 200mg 的单次总剂量，以研究结肠染色。还研究了美蓝的药代动力学和暴露于片剂后的安全性。使用 200mg 时，在升结肠和直肠乙状结肠（每个部位 75%的受试者）、横结肠和降结肠（每个部位约 63%的受试者）中获得了最佳染色，评估为可接受和良好染色的总和。没有报告任何受试者的任何感兴趣结肠区域没有染色或过度染色。在 100mg 剂量组中观察到了类似的结果。使用 100mg 时，美蓝血浓度的中位数达峰时间（T）为 12 小时，使用 200mg 时为 16 小时。使用 100mg 后 AUC 为 10.7±6.7μg/mLxh，使用 200mg 后 AUC 为 25.2±7.4μg/mLxh。在较低剂量后，半衰期范围为 9 至 22 小时，在较高剂量后半衰期范围为 6 至 26 小时。单次给药后，在肠道清洁准备的基础上，美蓝的累积尿液排泄量约为 100mg 后 28%，200mg 后 39%，直至 60 小时。单次给药后，与测试产品一起使用的肠道清洁准备的总体不良事件频率为 39%，但只有一个与测试产品相关：转氨酶异常。最常见的不良事件是短暂的多尿（17%）。一例严重不良事件（胃肠道出血）导致受试者停止研究并住院，另一例受试者因不良事件（呕血）退出研究。这两起事件都与美蓝无关。
