Department of Gastreonterology, IRCCS Istituto Clinico Humanitas, Milan, Italy.
Contemp Clin Trials. 2012 Mar;33(2):260-7. doi: 10.1016/j.cct.2011.11.006. Epub 2011 Nov 11.
Methylene blue-MMX tablets are proposed as colonic diagnostic staining. Methylene blue taken prior to colonoscopy is expected to provide an effective staining of colonic and rectal mucosa leaving unstained the dysplastic or polypoid areas. The present single dose, open-label study investigated the safety of methylene blue after single oral doses of 200 and 400mg in healthy volunteers. The absolute bioavailability was also investigated after the intake of 2L of bowel cleansing preparation in 2h and by comparing the dose of 200mg with a single iv dose of 100mg in the same subjects. Only non-serious adverse events occurred. Related events occurred to 8/22 subjects. Most of the events were mild and transient. Abnormal transaminases, gastrointestinal disorders and dysuria frequency were 13.6%. After intake of the laxative and the oral dose of 200mg, systemic exposure to methylene blue was shown in all subjects with concentrations increasing for 12h. The peak was reached in a median of 16 h. Peak blood concentration did not increase proportionally with the dose. AUC(0-t) was 32.94 μg/mL × h after 200mg and 38.08 μg/mL × h after 400mg. Half life ranged between 14 and 27 h after the lower dose and between 6 and 26 h after the higher dose. The cumulative excretion was about 40% of the injected dose, 39.67% after 200mg and 23.48% after 400mg. Absolute bioavailability of methylene blue calculated as ratio between AUC(0-t) oral/iv corrected for the dose was on average F(abs)=139.19 ± 52.00%.
亚甲蓝-MM 片剂被提议作为结肠诊断染色剂。预计结肠镜检查前服用的亚甲蓝能有效染色结肠和直肠黏膜，而未染色的异型增生或息肉样区域。本单次剂量、开放标签研究调查了健康志愿者单次口服 200mg 和 400mg 亚甲蓝的安全性。还在 2 小时内摄入 2L 肠道清洁准备后，以及在相同受试者中比较 200mg 剂量和单次静脉注射 100mg 剂量后，调查了绝对生物利用度。仅发生非严重不良事件。相关事件发生在 8/22 名受试者中。大多数事件为轻度和短暂的。异常转氨酶、胃肠道疾病和尿频频率为 13.6%。在服用泻药和 200mg 口服剂量后，所有受试者均显示出亚甲蓝的全身暴露，浓度在 12 小时内增加。中位数在 16 小时达到峰值。峰血浓度与剂量不成比例增加。200mg 后 AUC(0-t)为 32.94μg/mL×h，400mg 后为 38.08μg/mL×h。半衰期在较低剂量后在 14 至 27 小时之间，在较高剂量后在 6 至 26 小时之间。累积排泄量约为注射剂量的 40%，200mg 后为 39.67%，400mg 后为 23.48%。亚甲蓝的绝对生物利用度作为口服/静脉校正剂量后的 AUC(0-t)比值计算，平均 F(abs)=139.19±52.00%。
