What is lubiprostone?

Lubiprostone: A Chloride Channel Activator for Treating Constipation

Lubiprostone is an orally active prostaglandin analog that functions as a chloride channel activator to enhance intestinal fluid secretion, thereby improving bowel motility and alleviating constipation symptoms. 1, 2

Mechanism of Action

Lubiprostone works through a specific mechanism:

• Acts by specifically activating ClC-2 chloride channels located on the apical membrane of intestinal epithelial cells 1
• Increases chloride-rich intestinal fluid secretion without altering serum sodium and potassium concentrations 1
• Enhances gastrointestinal motility by increasing intestinal fluid content 1, 2
• Functions locally within the intestinal tract with minimal systemic absorption 3
• Bypasses the antisecretory action of opiates, making it effective for opioid-induced constipation 1

FDA-Approved Indications

Lubiprostone is approved for:

• Chronic idiopathic constipation (CIC) in adults at 24 mcg twice daily 2
• Irritable bowel syndrome with constipation (IBS-C) in women at 8 mcg twice daily 2
• Opioid-induced constipation (OIC) in adults with chronic non-cancer pain 4

Clinical Efficacy

Lubiprostone has demonstrated significant efficacy in clinical trials:

• Increases spontaneous bowel movements per week compared to placebo (mean difference 1.98) 2
• Improves stool consistency and reduces straining 2, 5
• Provides global relief of symptoms in IBS-C patients 2
• Effects typically manifest within 2 days in responders 2
• Shown to be effective for treating opioid-induced constipation 4
• Can be used in combination with peripherally acting μ-opioid receptor antagonists like methylnaltrexone for enhanced efficacy 4

Pharmacokinetics

• Rapidly metabolized with very low systemic bioavailability 1, 3
• Peak plasma concentrations of its active metabolite (M3) occur at approximately 1.1 hours 1
• Taking with food reduces peak concentration by 55% but doesn't affect overall absorption 1
• Approximately 94% bound to human plasma proteins 1

Dosing Considerations

• Available in two strengths: 8 mcg (pink capsules) and 24 mcg (orange capsules) 1
• For chronic idiopathic constipation: 24 mcg twice daily 2
• For IBS-C in women: 8 mcg twice daily 2
• Taking with food can reduce nausea, the most common side effect 2
• Dosage adjustment required for patients with moderate to severe hepatic impairment 1

Safety and Adverse Effects

• Most common side effect is nausea (up to 35% of patients) 2, 6
• Other common side effects include diarrhea, headache, and abdominal pain 6
• Nausea risk is dose-dependent and reduced when taken with food 2
• Minimal systemic absorption makes it relatively safe for long-term use 2
• No evidence of rebound constipation after discontinuation 5

Special Populations

• Safety profile in elderly patients (≥65 years) is consistent with the overall population 1
• Dosage adjustment required for patients with moderate to severe hepatic impairment 1
• No dosage adjustment needed for patients with mild hepatic impairment 1
• Well-tolerated for long-term use up to 13 months 2

Clinical Position

• Recommended by the British Society of Gastroenterology as an efficacious second-line drug for IBS-C 4
• The NCCN Palliative Care Panel recognizes lubiprostone as effective for opioid-induced constipation 4
• Less likely to cause diarrhea than other secretagogues but has higher incidence of nausea 4
• Can be used in combination with peripherally acting μ-opioid receptor antagonists for enhanced efficacy in opioid-induced constipation 4

Lubiprostone represents an important treatment option for various forms of constipation, particularly when first-line treatments are ineffective or poorly tolerated. Its local action in the intestine and minimal systemic absorption contribute to its favorable safety profile for long-term use.