Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome
Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome
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DOI：
10.1111/apt.13065
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发表时间：
2015-03-01
影响因子：
7.6
通讯作者：
Donato, L. J.
中科院分区：
文献类型：
--
作者：
Camilleri, M.;Acosta, A.;Donato, L. J.
研究背景约三分之一的IBS腹泻患者目的：评价胆汁酸螯合剂考来维仑对IBS-D中BA的粪便排泄、肝脏BA合成和腹泻的影响;评估个人或随机粪便样本是否准确反映了48-h总粪便胆汁酸排泄量和排泄的主要胆汁酸的比例，并研究对考来维仑反应的粪便脂肪排泄量。1875 mg [3片（625 mg片剂）]口服，每日两次，持续10天，共48小时粪便胆汁酸排泄和空腹血清C4（7 α-羟基-4-甾烯-3-酮;肝胆汁酸合成的替代物）。粪便日记记录了考来维仑治疗前8天和治疗期间8天的肠功能。结果考来维仑组大鼠粪便总胆汁酸和去氧胆酸排泄量显著增加，血清C4水平显著升高，粪便固体硬度显著增加。在治疗的最后48小时内，每周排便次数与排泄到粪便中的总胆汁酸呈显著负相关。随机粪便样本不能准确反映48小时总或个体粪便胆汁酸排泄。螯合胆汁酸的考来维仑没有增加粪便fat.ConclusionsColesevelam增加胆汁酸的粪便，同时改善粪便的一致性，并增加肝脏胆汁酸的合成，避免脂肪溢在IBS-D患者。总体效应与考来维仑的管腔胆汁酸螯合作用一致。
BackgroundAbout one-third of patients with IBS-diarrhoea (irritable bowel syndrome-D) have evidence of increased bile acid synthesis or excretion.AimsTo assess effects of the bile acid sequestrant, colesevelam, on faecal excretion of BAs, hepatic BA synthesis and diarrhoea in IBS-D; to appraise whether individual or random stool samples accurately reflect 48-h total faecal bile acid excretion and proportions of the main bile acids excreted and to study the faecal fat excretion in response to colesevelam.MethodsA single-centre, unblinded, single-dose trial of effects of colesevelam, 1875 mg [3 tablets (625 mg tablets)] orally, twice daily, for 10 days on total 48-h faecal bile acid excretion and fasting serum C4 (7 alpha-hydroxy-4-cholesten-3-one; surrogate of hepatic bile acid synthesis). Stool diaries documented bowel functions for 8 days prior and 8 days during colesevelam treatment. Stool 48-h samples and fasting serum were collected for faecal fat, faecal bile acid and serum C4.ResultsColesevelam was associated with significantly increased faecal total bile acid excretion and deoxycholic acid excretion, increased serum C4 and more solid stool consistency. There was a significant inverse correlation between number of bowel movements per week and the total bile acid sequestered into stool during the last 48 h of treatment. Random stool samples did not accurately reflect 48-h total or individual faecal bile acid excretion. Sequestration of bile acids by colesevelam did not increase faecal fat.ConclusionsColesevelam increases delivery of bile acids to stool while improving stool consistency, and increases hepatic bile acid synthesis, avoiding steatorrhoea in patients with IBS-D. Overall effects are consistent with luminal bile acid sequestration by colesevelam.