Abstract
Chronic constipation and IBS-C are two of the most common functional bowel disorders encountered by primary care providers and gastroenterologists, affecting up to 27% of the population in Western countries [1–4]. The treatment of these disorders is often empiric and most current therapies are indicated for episodic constipation. Over time, most patients become refractory to one or more laxatives. Lubiprostone (Amitiza) has been approved by the US Food and Drug Administration (FDA) for the treatment of chronic-idiopathic constipation [6]. It is an oral bicyclic fatty acid that selectively activates type 2 chloride channels in the apical membrane of the intestinal epithelial cells, hence stimulating chloride secretion, along with passive secretion of sodium and water, inducing peristalsis and laxation, without stimulating gastrointestinal smooth muscle. Several trials have shown it to be effective in the treatment of chronic idiopathic constipation, and recently also IBS-C. It has little systemic absorption and almost free of any serious adverse effects, however, occasionally can cause nausea. Based on the available evidence, it is reasonable to conclude that lubiprostone should be added to the short list of evidence-based pharmacotherapies for chronic constipation and IBS-C. Given the overlap between chronic constipation and IBS-C, clinicians can consider two strategies when deciding on the initial dose of lubiprostone. Based on current product labeling, it is recommended that 8 μg bid be started in patients with IBS-C whereas 24 μg bid be used in those with chronic constipation. Thus far, lubiprostone offers a novel approach to our therapeutic armamentarium, however, there is a need for more drugs with different mechanisms of action, in order to treat constipation that is often multifunctional.
Similar content being viewed by others
References
Drossman DA, Li Z, Andruzzi E, et al. US householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact. Dig Dis Sci. 1993;38:1569–1580.
Everhart JE, Go VL, Johannes RS, et al. A longitudinal survey of self-reported bowel habits in the United States. Dig Dis Sci. 1989;34:1153–1162.
Pare P, Ferrazzi S, Thompson WG, et al. An epidemiological survey of constipation in Canada: definitions, rates, demographics, and predictors of health care seeking. Am J Gastroenterol. 2001;96:3130–3137.
Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology. 2006;130:1480–1491.
Lau EM, Chan FK, Ziea ET, et al. Epidemiology of irritable bowel syndrome in Chinese. Dig Dis Sci. 2002;47:2621–2624.
Saito YA, Schoenfeld P, Locke GR III. The epidemiology of irritable bowel syndrome in North America: a systematic review. Am J Gastroenterol. 2002;97:1910–1915.
Brandt LJ, Prather CM, Quigley EM, et al. Systematic review on the management of chronic constipation in North America. Am J Gastroenterol. 2005;100:S5–S21.
Longstreth G, Thompson WG, Chey WD, et al. Functional bowel disorders. In: Drossman DA, Corazziari E, Delvaux M, et al., eds. Rome III: The Functional Gastrointestinal Disorders, First edn. McLean: Degnon Associates; 2006:487–555.
Lembo A, Camilleri M. Chronic constipation. N Engl J Med. 2003;349:1360–1368.
Rao SS, Tuteja AK, Vellema T, et al. Dyssynergic defecation: demographics, symptoms, stool patterns, and quality of life. J Clin Gastroenterol. 2004;38:680–685.
Rao SS. Dyssynergic defecation. Gastroenterol Clin North Am. 2001;30:97–114.
Johanson JF, Kralstein J. Chronic constipation: a survey of the patient perspective. Aliment Pharmacol Ther. 2007;25:599–608.
Bosshard W, Dreher R, Schnegg JF, et al. The treatment of chronic constipation in elderly people: an update. Drugs Aging. 2004;21:911–930.
Tuteja AK, Talley NJ, Joos SK, et al. Is constipation associated with decreased physical activity in normally active subjects? Am J Gastroenterol. 2005;100:124–129.
Ramkumar D, Rao SS. Efficacy and safety of traditional medical therapies for chronic constipation: systematic review. Am J Gastroenterol. 2005;100:936–971.
Jones MP, Talley NJ, Nuyts G, et al. Lack of objective evidence of efficacy of laxatives in chronic constipation. Dig Dis Sci. 2002;47:2222–2230.
Tramonte SM, Brand MB, Mulrow CD, et al. The treatment of chronic constipation in adults. A systematic review. J Gen Intern Med. 1997;12:15–24.
Chapman RW, Sillery J, Fontana DD, et al. Effect of oral dioctyl sodium sulfosuccinate on intake-output studies of human small and large intestine. Gastroenterology. 1985;89:489–493.
Fain AM, Susat R, Herring M, et al. Treatment of constipation in geriatric and chronically ill patients: a comparison. South Med J. 1978;71:677–680.
Xing JH, Soffer EE. Adverse effects of laxatives. Dis Colon Rectum. 2001;44:1201–1209.
Bass P, Dennis S. The laxative effects of lactulose in normal and constipated subjects. J Clin Gastroenterol. 1981;3(Suppl 1):23–28.
Schiller LR. Review article: the therapy of constipation. Aliment Pharmacol Ther. 2001;15:749–763.
Stewart WF, Liberman JN, Sandler RS, et al. Epidemiology of constipation (EPOC) study in the United States: relation of clinical subtypes to sociodemographic features. Am J Gastroenterol. 1999;94:3530–3540.
Singh G, Lingala V, Wang H, et al. Use of health care resources and cost of care for adults with constipation. Clin Gastroenterol Hepatol. 2007;5:1053–1058.
Lipecka J, Bali M, Thomas A, et al. Distribution of ClC-2 chloride channel in rat and human epithelial tissues. Am J Physiol Cell Physiol. 2002;282:C805–C816.
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:C1173–C1183.
Jentsch TJ. CLC chloride channels and transporters: from genes to protein structure, pathology and physiology. Crit Rev Biochem Mol Biol. 2008;43:3–36.
Thiagarajah JR, Broadbent T, Hsieh E, et al. Prevention of toxin-induced intestinal ion and fluid secretion by a small-molecule CFTR inhibitor. Gastroenterology. 2004;126:511–519.
Camilleri M, Bharucha AE, Ueno R, et al. Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers. Am J Physiol Gastrointest Liver Physiol. 2006;290:G942–G947.
Camilleri M, Gorman H. Intestinal permeability and irritable bowel syndrome. Neurogastroenterol Motil. 2007;19:545–552.
Moeser AJ, Haskell MM, Shifflett DE, et al. ClC-2 chloride secretion mediates prostaglandin-induced recovery of barrier function in ischemia-injured porcine ileum. Gastroenterology. 2004;127:802–815.
Cuppoletti J, Malinowska DH, Chakrabarti J, et al. Effects of lubiprostone on human uterine smooth muscle cells. Prostaglandins Other Lipid Mediat. 2008;86:56–60.
Mizumori M, Akiba Y, Kaunitz JD. Lubiprostone stimulates duodenal bicarbonate secretion in rats. Dig Dis Sci. 2009;54:2063–2069.
Johanson JF, Drossman DA, Panas R, et al. Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2008;27:685–696.
Thompson WG, Longstreth G, Drossman DA, Heaton K, Irvine EJ, Muller-Lissner S. Book chapter—functional bowel disorders and functional abdominal pain. In: Drossman DA, Corazziari E, Talley NJ, et al., eds. The Functional Gastrointestinal Disorders. 2nd ed. McLean: Degnon Associates; 2000:351–432.
Drossman DA, Chey WD, Johanson JF, et al. Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome–results of two randomized, placebo-controlled studies. Aliment Pharmacol Ther. 2009;29:329–341.
Patrick DL, Drossman DA, Frederick IO, et al. Quality of life in persons with irritable bowel syndrome: development and validation of a new measure. Dig Dis Sci. 1998;43:400–411.
Irvine EJ, Ferrazzi S, Pare P, et al. Health-related quality of life in functional GI disorders: focus on constipation and resource utilization. Am J Gastroenterol. 2002;97:1986–1993.
Dennison C, Prasad M, Lloyd A, et al. The health-related quality of life and economic burden of constipation. Pharmacoeconomics. 2005;23:461–467.
Talley NJ, Weaver AL, Zinsmeister AR, et al. Onset and disappearance of gastrointestinal symptoms and functional gastrointestinal disorders. Am J Epidemiol. 1992;136:165–177.
Talley NJ, Zinsmeister AR, Van Dyke C, Melton LJ. Epidemiology of colonic symptoms and the irritable bowel syndrome. Gastroenterology. 1991;101:927–934.
Saito YA, Locke GR, Talley NJ, et al. A comparison of the Rome and Manning criteria for case identification in epidemiological investigations of irritable bowel syndrome. Am J Gastroenterol. 2000;95:2816–2824.
Luscombe FA. Health-related quality of life and associated psychosocial factors in irritable bowel syndrome: a review. Qual Life Res. 2000;9:161–176.
Sandler RS, Everhart JE, Donowitz M, et al. The burden of selected digestives diseases in the United States. Gastroenterology. 2002;122:1500–1511.
Levy RL, Von Korff M, Whitehead WE, et al. Costs of care for irritable bowel syndrome patients in a health maintenance organization. Am J Gastroenterol. 2001;96:3122–3129.
Brandt LJ, Prather CM, Quigley EMM, et al. Systematic review on the management of chronic constipation in North America. Am J Gastroenterol. 2005;100:S5–S22.
Young RJ, Beerman LE, Vanderhoof JA. Increasing oral fluids in chronic constipation in children. Gastroenterol Nurs. 1998;21:156–161.
Barish CF, Drossman D, Johanson JF, Ueno R. Efficacy and safety of lubiprostone in patients with chronic constipation. Dig Dis Sci. 2010;55:1090–1097.
Fei G, Raehal K, Liu S, et al. Lubiprostone reverses the inhibitory action of morphine on intestinal secretion in guinea pig and mouse. Pharmacol Exp Ther. 2010;334:333–340.
O’Brien CE, Anderson PJ, Stowe CD. Use of the chloride channel activator lubiprostone for constipation in adults with cystic fibrosis: a case series. Ann Pharmacother. 2010;44:577–581.
Ueno R. Multiple, escalating, oral-dose study to assess the safety, tolerance and pharmacodynamic profile of lubiprostone in normal healthy volunteers. Neurogastroenterol Motil. 2005;17:A78.
Kapoor S. Lubiprostone: clinical applications beyond constipation. World J Gastroenterol. 2009;15:1147.
De Lisle RC, Mueller R, Roach E. Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype. BMC Gastroenterol. 2010;10:107.
Johanson JF, Panas R, Holland PC, et al. Long-term efficacy of lubiprostone for the treatment of chronic constipation. Gastroenterology. 2006;130:A317.
Kaltoft N, Tilotta MC, Witte AB, et al. Prostaglandin E2-induced colonic secretion in patients with and without colorectal neoplasia. BMC Gastroenterol. 2010;10:9.
Sun X, Wang X, Wang GD, et al. Lubiprostone reverses the inhibitory action of morphine on mucosal secretion in human small intestine. Dig Dis Sci. 2011;56:330–338.
Sweetser S, Busciglio IA, Camilleri M, et al. Effect of a chloride channel activator, lubiprostone, on colonic sensory and motor functions in healthy subjects. Am J Physiol Gastrointest Liver Physiol. 2009;296:G295–G301.
Wood JD. Enteric nervous system: sensory physiology, diarrhea, and constipation. Curr Opin Gastroenterol. 2010;26:102–108.
FDA Center for Drug Evaluation and Research (CDER)—April 2008.
Bijvelds MJ, Bot AG, Escher JC, De Jonge HR. Activation of intestinal Cl-secretion by lubiprostone requires the cystic fibrosis transmembrane conductance regulator. Gastroenterology. 2009;137:976–985.
Bao HF, Li L, Self J, et al. A synthetic prostone activates apical chloride channels in A6 epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2009;295:G234–G251.
Lunsford TN, Harris LA. Lubiprostone: evaluation of the newest medication for the treatment of adult women with constipation-predominant irritable bowel syndrome. Int J Womens Health. 2010;2:361–374.
Joo NS, Wine JJ, Cuthbert AW. Lubiprostone stimulates secretion from tracheal submucosal glands of sheep, pigs and humans. Am J Physiol Lung Cell Mol Physiol. 2009;296:L811–L824.
Lubiprostone (Amitiza®) (Sucampo Pharmaceuticals. Chicago, IL: Bethesda & Takeda Pharmaceuticals of North America) —Package insert.
Acknowledgments
Dr. Satish Rao is supported by NIH grant RO1 DK 57100-05.
Conflict of interest
The authors disclose no conflicts.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Schey, R., Rao, S.S.C. Lubiprostone for the Treatment of Adults with Constipation and Irritable Bowel Syndrome. Dig Dis Sci 56, 1619–1625 (2011). https://doi.org/10.1007/s10620-011-1702-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-011-1702-2