Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis.
Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis.
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DOI：
10.1053/j.gastro.2010.07.052
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发表时间：
2010-11
期刊：
影响因子：
29.4
通讯作者：
Zinsmeister AR
中科院分区：
文献类型：
--
作者：
Rao AS;Wong BS;Camilleri M;Odunsi-Shiyanbade ST;McKinzie S;Ryks M;Burton D;Carlson P;Lamsam J;Singh R;Zinsmeister AR
鹅脱氧胆酸钠（CDC）在健康中加速结肠运输。我们的目的是检查CDC在便秘型肠易激综合征（IBS-C）中的药效学（结肠运输，肠功能）和药物遗传学。在一项双盲安慰剂对照研究中，36名女性IBS-C患者被随机分为缓释口服安慰剂、500 mg CDC或1000 mg CDC治疗4天。我们评估了胃肠道和结肠转运、粪便特征以及转运与空腹血清7αC4（胆汁酸合成替代物）和FGF19（胆汁酸合成负调节因子）水平的关系。我们分析了36例IBS-C患者和57名健康志愿者中参与胆汁酸合成调控的候选遗传多态性，以评估遗传对CDC转运效应的影响。与安慰剂相比，CDC组整体结肠运输和升结肠排空（act1 / 2）显著加快（P = 0.005和P = 0.028）。与安慰剂相比，CDC组的大便一致性更松散（P = 0.003），大便频率增加（P = 0.018），更容易通过（P = 0.024）。最常见的副作用是下腹部绞痛/疼痛（P = 0.01）。空腹血清7αC4（而非FGF19）与结肠运输呈正相关（rs = 0.749, P = 0.003，安慰剂组）。FGFR4基因变异与CDC患者的act1 / 2相关（未校正P = 0.015）；α - klothoβ变异显示基于患者亚组的基因-治疗相互作用（未校正P = 0.0088）。CDC加速了女性IBS-C患者的结肠运输并改善了肠道功能。胆汁酸的合成速度影响结肠转运。胆汁酸合成负反馈抑制的遗传变异可能影响cdc介导的结肠转运加速。
Sodium chenodeoxycholate (CDC) accelerates colonic transit in health. Our aim was to examine pharmacodynamics (colonic transit, bowel function) and pharmacogenetics of CDC in constipation-predominant irritable bowel syndrome (IBS-C). In a double-blind placebo-controlled study, 36 female patients with IBS-C were randomized to treatment with delayed-release oral formulations of placebo, 500 mg CDC, or 1000 mg CDC for 4 days. We assessed gastrointestinal and colonic transit, stool characteristics, and associations of transit with fasting serum 7αC4 (surrogate of bile acid synthesis) and FGF19 (negative regulator of bile acid synthesis) levels. Candidate genetic polymorphisms involved in regulation of bile acid synthesis were analyzed in the 36 patients with IBS-C and 57 healthy volunteers to assess genetic influence on effects of CDC on transit. Overall colonic transit and ascending colon emptying (AC t½) were significantly accelerated in the CDC group compared with placebo (P = .005 and P = .028, respectively). Looser stool consistency (P = .003), increased stool frequency (P = .018), and greater ease of passage (P = .024) were noted with CDC compared with placebo. The most common side effect was lower abdominal cramping/pain (P = .01). Fasting serum 7αC4 (but not FGF19) was positively associated with colonic transit (rs = 0.749, P = .003, placebo group). Genetic variation in FGFR4 was associated with AC t½ in response to CDC (uncorrected P = .015); αKlothoβ variant showed a gene-by-treatment interaction based on patient subgroup (uncorrected P = .0088). CDC accelerates colonic transit and improves bowel function in female patients with IBS-C. The rate of bile acid synthesis influences colonic transit. Genetic variation in negative feedback inhibition of bile acid synthesis may affect CDC-mediated acceleration of colonic transit.
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影响因子：
15.9
作者：
MEKHJIAN, HS;PHILLIPS, SF;HOFMANN, AF
通讯作者：
HOFMANN, AF
DOI：
10.1016/j.cgh.2009.10.020
发表时间：
2010-02
期刊：
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
影响因子：
--
作者：
Odunsi-Shiyanbade ST;Camilleri M;McKinzie S;Burton D;Carlson P;Busciglio IA;Lamsam J;Singh R;Zinsmeister AR
通讯作者：
Zinsmeister AR
DOI：
10.1007/bf01072128
发表时间：
1976-01-01
期刊：
AMERICAN JOURNAL OF DIGESTIVE DISEASES
影响因子：
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作者：
CONLEY, DR;COYNE, MJ;SCHOENFIELD, LJ
通讯作者：
SCHOENFIELD, LJ
影响因子：
1.9
作者：
Abrahamsson, Hasse;Ostlund-Lindqvist, Ann-Margret;Gillberg, Per-Goran
通讯作者：
Gillberg, Per-Goran
DOI：
10.1152/ajpgi.00194.2001
发表时间：
2002-03-01
影响因子：
4.5
作者：
Bampton, PA;Dinning, PG;Cook, IJ
通讯作者：
Cook, IJ