Gunput M D
Glaxo Wellcome Research and Development, Greenford, Middlesex, UK.
Aliment Pharmacol Ther. 1999 May;13 Suppl 2:70-6. doi: 10.1046/j.1365-2036.1999.00009.x.
Alosetron, a new 5-HT3 antagonist is in development for the treatment of the irritable bowel syndrome. A series of randomized placebo-controlled double-blind clinical pharmacology studies have been performed in healthy volunteers and irritable bowel syndrome patients to evaluate the pharmacokinetics and some of the pharmacodynamic properties of this drug. Alosetron was shown to dose-dependently inhibit the 5-HT-induced skin flare response, increase colonic transit time and increase basal jejunal water and electrolyte absorption, in healthy volunteers. In irritable bowel syndrome patients, alosetron increased colonic compliance. Alosetron had no effect on the perception of gastric distension or on meal-stimulated gastric acid secretion. Orally alosetron has approximately 60% bioavailability and a half-life of 1.5 h. At doses of 1 mg or more, it has a pharmacodynamic duration of action which justifies twice a day dosing. These data support the potential use of alosetron in the treatment of irritable bowel syndrome.
阿洛司琼是一种新型5-羟色胺3（5-HT3）拮抗剂，正处于研发阶段，用于治疗肠易激综合征。已在健康志愿者和肠易激综合征患者中进行了一系列随机、安慰剂对照、双盲临床药理学研究，以评估该药物的药代动力学和一些药效学特性。在健康志愿者中，阿洛司琼显示出剂量依赖性地抑制5-羟色胺诱导的皮肤潮红反应、增加结肠转运时间以及增加空肠基础水和电解质吸收。在肠易激综合征患者中，阿洛司琼增加了结肠顺应性。阿洛司琼对胃扩张的感知或进餐刺激的胃酸分泌没有影响。口服阿洛司琼的生物利用度约为60%，半衰期为1.5小时。在1毫克或更高剂量时，其药效学作用持续时间证明每日给药两次是合理的。这些数据支持阿洛司琼在治疗肠易激综合征方面的潜在用途。
