与alosetron药理学和临床经验。
文章的细节
-
引用
复制到剪贴板 -
卡米尔米
与alosetron药理学和临床经验。
专家当今Investig药物。2000年1月,9 (1):147 - 59。
- PubMed ID
-
11060667 (在PubMed]
- 文摘
-
Alosetron (Lotronex)是一种强有力的、高度选择性5 -(3)拮抗剂。动物模型表明,它是活跃在焦虑、精神病、认知障碍、呕吐和停药,虽然在人类中的应用已经几乎完全局限于肠易激综合症(IBS)。Alosetron不会引起不利的药效学作用,口服后吸收迅速,广泛分布在组织后口头或承运动物的剂量。新陈代谢是快速和广泛的与去甲基羟基化和氧化。药物,或其两个主要代谢产物,同样通过胆道和肾脏排泄。Alosetron证明安全的毒性研究;在高重复剂量,临床症状是瞬态和重复对生育没有明显的不利影响,繁殖性能或胎儿发育。在药代动力学研究中,生物利用度的alosetron健康志愿者大约是60%,血浆半衰期约为1.5 h。有一些性别差异在药动学特征,与alosetron浓度雌性高30 - 50%。beplayapp的不一致的差异alosetron观察年轻人和老年人之间的血清浓度。单一的药物动力学,口服剂量的alosetron线性8毫克。 In human pharmacodynamic studies, alosetron increased basal jejunal water and electrolyte absorption, increased colonic transit time and, consequently, whole gut transit time. Alosetron has been evaluated in two large Phase II trials (randomised, double-blinded, placebo-controlled) and in Phase III trials which included a four-week observation period after cessation. Dose response studies suggested that the effective dosages could be between 1 and 2 mg, twice-daily. In Phase II trials, alosetron, 1 mg b.i.d., resulted in a greater proportion of non-constipated IBS patients reporting adequate relief of pain and discomfort, as well as improvement of bowel symptoms, frequency, urgency and stool consistency when compared with placebo. However, this beneficial effect was seen exclusively among females. Phase III studies evaluated exclusively females with non-constipated IBS and confirmed the results of the Phase II studies. Alosetron was well-tolerated in all studies, with the most frequently recorded adverse event being constipation. Thus, alosetron appears promising in the treatment of abdominal pain and discomfort and normalising of bowel function in patients with non-constipated IBS. It also improves quality of life, has a high degree of tolerability and has an excellent safety profile to date.