S1301 The IBAT Inhibition by A3309 – A Potential Mechanism for the Treatment of Constipation

Gillberg, Per‐Göran; Dahlström, Mikael; Starke, Ingemar; Östlund-Lindqvist, Ann-Margret

doi:10.1016/s0016-5085(10)61017-7

Cited by 24 publications

(27 citation statements)

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“…A3309 is a potent and selective inhibitor of IBAT and reduces meat‐induced constipation in dogs 14 . Animal experiments show that A3309 has a minimal systemic exposure and a high protein binding (>99%).…”

Section: Introductionmentioning

confidence: 99%

Randomised clinical trial: the ileal bile acid transporter inhibitor A3309 vs. placebo in patients with chronic idiopathic constipation - a double-blind study

Simrén

Bajor

Gillberg

et al. 2011

Alimentary Pharmacology &Amp; Therapeutics

101

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Section: Introductionmentioning

confidence: 99%

Randomised clinical trial: the ileal bile acid transporter inhibitor A3309 vs. placebo in patients with chronic idiopathic constipation - a double-blind study

Simrén

Bajor

Gillberg

et al. 2011

Alimentary Pharmacology &Amp; Therapeutics

101

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“…Due to the complexity of GI motility disorders, many novel therapies targeting different receptors are currently under investigation in both human and animal studies. These receptors include type‐2 chloride channel activators, CCK receptor antagonists, guanylate cyclase 2C agonists, and ileal bile acid transporter antagonists . Lubiprostone, a type‐2 chloride channel (CIC‐2) activator, activates chloride receptors located on gut epithelial cells and drives chloride ions into the gut lumen, inducing intestinal fluid secretion and increasing intestinal motility .…”

Section: Specific Pharmacological Interventionsmentioning

confidence: 99%

“…Ileal bile acid transporter inhibitors act locally in the gut to inhibit the reuptake of bile acids and, in turn, increase motility. A3309, an ileal bile acid transporter, has been shown to decrease constipation and ileus in a dog experimental model …”

Section: Specific Pharmacological Interventionsmentioning

confidence: 99%

Gastrointestinal dysmotility disorders in critically ill dogs and cats

Whitehead

Cortes

Eirmann

2016

J Vet Emergen Crit Care

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Objective -To review the human and veterinary literature regarding gastrointestinal (GI) dysmotility disorders in respect to pathogenesis, patient risk factors, and treatment options in critically ill dogs and cats. Etiology -GI dysmotility is a common sequela of critical illness in people and small animals. The most common GI motility disorders in critically ill people and small animals include esophageal dysmotility, delayed gastric emptying, functional intestinal obstruction (ie, ileus), and colonic motility abnormalities. Medical conditions associated with the highest risk of GI dysmotility include mechanical ventilation, sepsis, shock, trauma, systemic inflammatory response syndrome, and multiple organ failure. The incidence and pathophysiology of GI dysmotility in critically ill small animals is incompletely understood. Diagnosis -A presumptive diagnosis of GI dysmotility is often made in high-risk patient populations following detection of persistent regurgitation, vomiting, lack of tolerance of enteral nutrition, abdominal pain, and constipation. Definitive diagnosis is established via radioscintigraphy; however, this diagnostic tool is not readily available and is difficult to perform on small animals. Other diagnostic modalities that have been evaluated include abdominal ultrasonography, radiographic contrast, and tracer studies. Therapy -Therapy is centered at optimizing GI perfusion, enhancement of GI motility, and early enteral nutrition. Pharmacological interventions are instituted to promote gastric emptying and effective intestinal motility and prevention of complications. Promotility agents, including ranitidine/nizatidine, metoclopramide, erythromycin, and cisapride are the mainstays of therapy in small animals. Prognosis -The development of complications related to GI dysmotility (eg, gastroesophageal reflux and aspiration) have been associated with increased mortality risk. Institution of prophylaxic therapy is recommended in high-risk patients, however, no consensus exists regarding optimal timing of initiating prophylaxic measures, preference of treatment, or duration of therapy. The prognosis for affected small animal patients remains unknown. (J Vet Emerg

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“…Conversely, administration of delayed-release chenodeoxycholate, 1g/day, to the colon of healthy volunteers (102) and patients with IBS-C (103) accelerated colonic transit, loosened stool consistency, and reduced straining over a short-term trial. An extension of this principle is to deliver more endogenous bile acids to the colon by inhibiting the ileal bile acid transporter (104). This agent has been tested in phase IIA and IIB trials in patients with chronic idiopathic constipation and functional constipation, and all studies provide concordant information: acceleration of colonic transit; increased stool frequency, and relief of symptoms associated with constipation such as discomfort and bloating (105–107).…”

Section: Bile Acid Modulationmentioning

confidence: 99%

Brain‐Gut Axis

Camilleri

Lorenzo

2012

J. pediatr. gastroenterol. nutr.

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The present review describes advances in understanding the mechanisms and provide an update of present and promising therapy directed at the gut or the brain in the treatment of irritable bowel syndrome (IBS). The diagnosis of IBS typically is based on identification of symptoms, such as the Rome III criteria for IBS in adults and children. The criteria are similar in children and adults. The focus of the present review is the bowel dysfunction associated with IBS.

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S1301 The IBAT Inhibition by A3309 – A Potential Mechanism for the Treatment of Constipation

Cited by 24 publications

References 0 publications

Randomised clinical trial: the ileal bile acid transporter inhibitor A3309 vs. placebo in patients with chronic idiopathic constipation - a double-blind study

Randomised clinical trial: the ileal bile acid transporter inhibitor A3309 vs. placebo in patients with chronic idiopathic constipation - a double-blind study

Gastrointestinal dysmotility disorders in critically ill dogs and cats

Brain‐Gut Axis

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