Lubiprostone: evaluation of the newest medication for the treatment of adult women with constipation-predominant irritable bowel syndrome

Figures & data

Table 1 Definition of IBS – American College of Gastroenterology and Rome III definition with Bristol Stool Form Scale

American College of Gastroenterology

Rome III definition

Abdominal pain or discomfort associated with altered bowel function without evidence of biochemical or structural abnormality.

IBS with constipation (IBS-C) – hard or lumpy stools* ≥25% and loose (mushy) or watery stools† <25% of bowel movements.‡ IBS with diarrhea (IBS-D) – loose (mushy) or watery stools† ≥25% and hard or lumpy stool* <25% of bowel movements.‡ Mixed IBS (IBS-M) – hard or lumpy stools* ≥25% and loose (mushy) or watery stools† ≥25% of bowel movements.‡ Unsubtyped IBS (IBS-U) – insufficient abnormality of stool consistency to meet criteria IBS-C, D or M.‡

* Bristol Stool Form Scale 1–2 [separate hard lumps like nuts (difficult to pass) or sausage shaped but lumpy];

† Bristol Stool Form Scale 6–7 (fluffy pieces with ragged edges, a mushy stool or watery, no solid pieces, entirely liquid);

‡ In the absence of use of antidiarrheals or laxatives.

**† Criteria must have been present for at least 3 days out of the past 3 months and have an onset >6 months before diagnosis.

Table

Table

The Bristol Stool Form Scale
Type	Description
1.	Separate hard lumps like nuts (difficult to pass)
2.	Sausage shaped but lumpy
3.	Like sausage but with cracks on its surface
4.	Like sausage or snake, smooth and soft
5.	Soft blobs with clear cut edges (passed easily)
6.	Fluffy pieces with ragged edges, a mushy stool
7.	Watery, no solid pieces, entirely liquid

Figure 1 Chemical structure of lubiprostone (RU-0211) (C₂₀H₃₂F₂O₅).

Note: Drug bank: accession number DB01046; CAS registry number 136790-76-6.

Figure 2 Mechanism of action of lubiprostone across the intestinal epithelial cell. Copyright ©2004. Adapted with permission from American Physiological Society. Cuppoletti J, Malinowska DH, Tewari KP, et al. SPI-0211 activates T84 cell chloride transport and recombinant human ClC-2 chloride currents. Am J Physiol Cell Physiol. 2004;287(5):C1173–C1183.

Abbreviations: Cl⁻, chloride; H₂O, water; K⁺, potassium; Na⁺, sodium; ClC-2, type 2 chloride channel.

Table 2 Safety profile of lubiprostone compared in chronic constipation and IBS-C in phase II and phase III trials

Symptom	Placebo ^*CC N = 346 (%)	Lubiprostone 24 μg twice daily N = 1113 (%)	Placebo ^**IBS N = 435 (%)	Lubiprostone 8 μg twice daily N = 1011 (%)
Nausea	16 (5.1)	346 (31.1)	17 (4)	81 (8)
Diarrhea	3 (0.9)	147 (13.2)	17 (4)	71 (7)
Headache	21 (6.6)	147 (13.2)	No reported	Not reported
Abdominal distention	9 (2.2)	79 (7.1)	22 (5)	50 (5)
Abdominal pain	7 (2.8)	75 (6.7)	9 (2)	30 (3)
Flatulence	6 (1.9)	68 (6.1)	Not reported	Not reported
Vomiting	3 (0.9)	51(4.6)	Not reported	Not reported
Dizziness	4 (1.3)	46 (4.1)	Not reported	Not reported