Crofelemer, a Novel Agent for Treatment of Secretory Diarrhea
Crofelemer, a Novel Agent for Treatment of Secretory Diarrhea
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DOI：
10.1345/aph.1m658
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发表时间：
2010-05-01
影响因子：
2.9
通讯作者：
Garey, Kevin W.
中科院分区：
文献类型：
--
作者：
Crutchley, Rustin D.;Miller, Jennifer;Garey, Kevin W.
目的：对克罗非美尔的化学、药理、药代动力学、疗效和安全性进行综述。数据来源：应用PubMed(截至2010年4月)、Google Scholar和部分Ovid书目检索文献，检索词SP-303、PROVIR和CROFELEMER。DATA摘录：与克罗非勒姆的安全性和有效性相关的体外英语和临床研究。DATA综合：克罗非勒胺是一种一流的药物，可能对不同类型的分泌性腹泻有用，因为它通过直接抑制两种不同的肠道氯离子通道来阻止氯化物和液体分泌到肠道。与安慰剂治疗的患者相比，CroFelemer显著地使旅行者腹泻患者的症状缓解更快，同时治疗失败率更低。在一项特殊的分析中，与安慰剂相比，克罗非莱姆似乎还减少了艾滋病相关腹泻患者的异常粪便重量和频率。在第三项试验中，克罗非勒姆在治疗12周后对腹泻型肠易激综合征患者的大便一致性没有显著改善。然而，女性患者的无痛天数显著增加。初步研究还表明，克罗非勒姆可能会减少霍乱等感染性腹泻患者的水样粪便排出量。在临床试验中，克罗非莱姆的耐受性似乎很好，不良反应与安慰剂相当。结论：克罗非勒姆具有一种新的作用机制，在治疗多种原因的分泌性腹泻方面显示出良好的前景。然而，为了充分评估该药的有效性和安全性，仍需进一步的3期临床试验的结果。
OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics, efficacy, and safety of crofelemer.DATA SOURCES: A literature search using the terms SP-303, Provir, and crofelemer was performed with PubMed (up to April 2010), Google Scholar, and selected Ovid bibliography searches. Additional references from the bibliographies of articles included in the search, as well as company and Food and Drug Administration Web sites, were also assessed.DATA EXTRACTION: English-language in vitro and clinical studies associated with the safety and efficacy of crofelemer were included.DATA SYNTHESIS: Crofelemer is a first-in-class agent that may be useful for different types of secretory diarrhea, since it prevents chloride and fluid secretion into the bowel by directly inhibiting 2 distinct intestinal chloride channels. Crofelemer significantly brought about faster symptom resolution in patients with traveler's diarrhea, along with lower rates of treatment failure compared to placebo-treated patients. In a post hoc analysis, crofelemer compared to placebo also appears to have reduced abnormal stool weight and frequency in patients with AIDS-associated diarrhea. In a third trial, crofelemer did not offer a significant benefit in improving stool consistency after 12 weeks of treatment in patients with diarrhea-predominant irritable bowel syndrome. However, a significant increase in pain-free days was noted in female patients. Preliminary studies also show that crofelemer may reduce watery stool output in patients with infectious diarrhea such as cholera. Oral crofelemer seemed to be well tolerated in clinical trials, with adverse effect profiles comparable to those with placebo.CONCLUSIONS: Crofelemer possesses a novel mechanism of action that shows promise in treating secretory diarrhea of several etiologies. However, results from further Phase 3 clinical trials are still needed in order to fully evaluate the efficacy and safety of this agent.