Layer P H, Goebell H, Keller J, Dignass A, Klotz U
Department of Medicine, University of Essen, Germany.
Gastroenterology. 1995 May;108(5):1427-33. doi: 10.1016/0016-5085(95)90691-6.
BACKGROUND/AIMS: Oral use of mesalamine in inflammatory bowel disease requires slow-release preparations to prevent premature absorption and inactivation. Resulting luminal concentrations within the human small intestine are unknown. The aim of this study was to determine human intestinal delivery patterns of mesalamine from a microgranule preparation (Pentasa; Ferring Arzeimittel, Kiel, Germany) effective in Crohn's disease with small bowel involvement.
A multilumen tube for duodenal, jejunal, and ileal aspiration and marker perfusion was placed in 6 normal subjects. Levels of luminal, plasma, and urinary mesalamine and its main metabolite, acetyl mesalamine, were measured for 7 hours after ingestion of mesalamine (500 mg) with a labeled meal.
Gastric emptying of mesalamine paralleled the meal, and its release occurred throughout the small intestine (cumulative, 20% of dose). For 4 hours, mean luminal mesalamine and acetyl mesalamine concentrations were 52 and 38 micrograms/mL (duodenum), 59 and 82 micrograms/mL (jejunum), and 64 and 104 micrograms/mL (ileum). Cumulative colonic delivery was 82% (7% dissolved, 75% in microgranules), and urinary excretion was 3.5%.
Although the major part of continuous-release mesalamine is delivered to the colon, large proportions are liberated and available at high concentrations within the small intestinal lumen, thus explaining its therapeutic efficacy in small intestinal Crohn's disease.
背景/目的：在炎症性肠病中口服美沙拉嗪需要缓释制剂以防止药物过早吸收和失活。人体小肠内的药物浓度尚不清楚。本研究的目的是确定一种对累及小肠的克罗恩病有效的微颗粒制剂（颇得斯安；德国基尔费林制药）中美沙拉嗪的人体肠道释放模式。
将一根用于十二指肠、空肠和回肠抽吸及标记物灌注的多腔管置于6名正常受试者体内。在服用含标记物的美沙拉嗪（500毫克）后7小时，测量肠腔、血浆和尿液中美沙拉嗪及其主要代谢产物乙酰美沙拉嗪的水平。
美沙拉嗪的胃排空与食物同步，其在整个小肠内释放（累积释放剂量的20%）。在4小时内，十二指肠中美沙拉嗪和乙酰美沙拉嗪的平均肠腔浓度分别为52和38微克/毫升，空肠中为59和82微克/毫升，回肠中为64和104微克/毫升。结肠累积释放率为82%（7%溶解，75%存在于微颗粒中），尿排泄率为3.5%。
尽管缓释美沙拉嗪的大部分药物被输送至结肠，但仍有很大比例在小肠肠腔内以高浓度释放并可被利用，这就解释了其在小肠克罗恩病中的治疗效果。
