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Latest Research on Constipation
     
Int J Clin Pharmacol Ther. 2008 Feb;Volume 46(Februar):89-95.
OTC laxative use of sodium picosulfate â results of a pharmacy-based patient survey (cohort study).
Hinkel U, Schuijt C, Erckenbrecht JF.
1Boehringer Ingelheim GmbH, Ingelheim and 2Florence Nightingale Hospital, Düsseldorf-Kaiserswerth, Germany.

Objectives: Constipation is one of the most frequent gastrointestinal symptoms. Traditionally, drug therapy for constipation is not prescribed and controlled by physicians. Instead, laxatives are sold by pharmacists as over-the-counter (OTC) medication. The aim of this study was to explore the safety and usage pattern of the OTC laxative sodium picosulfate use by collecting data from patients at their pharmacies. The study describes how self-treatment of constipation is practiced. In addition, the characteristics of patients buying the contact laxative, sodium picosulfate, for self-treatment of constipation were analyzed. Methods: The survey was a pharmacy-based observational study (PHOBS) in community pharmacies in Germany. Participating pharmacists asked customers requesting a specific contact laxative to participate in the study. Customers gave verbal informed consent to study participation before receiving a structured questionnaire to be completed at home and then returned to the pharmacy. Results: Data from 1,845 patients recruited by 243 pharmacies were collected. Compliance with the recommended dosage of 5 â 10 mg/day was 96%, compliance with the indication of constipation was 99%. More than 90% rated the efficacy as âvery goodâ to âgoodâ. There was no weakening of the efficacy rating with increasing duration of use. 8% of patients reported mild-to-moderate adverse events. Nearly 60% of respondents reported to be satisfied with less than 1 bowel movement per day. Therefore, users appear to have a rational way of using OTC laxatives. Conclusions: Self-medication of constipation with sodium picosulfate is efficacious and considered to be safe.

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Support Care Cancer. 2008 Jan 16 [Epub ahead of print]
Constipation in cancer patients on morphine.
Droney J, Ross J, Gretton S, Welsh K, Sato H, Riley J.
Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK, jodroney@hotmail.com.

GOALS OF WORK: Constipation is a significant problem in patients taking morphine for cancer pain. The aims of this study were (1) to assess the magnitude of constipation in this study cohort, (2) to analyse the constipation treatment strategies and (3) to look for evidence of inter-individual variation in both susceptibility to constipation and response to treatment with laxatives in this patient group. MATERIALS AND METHODS: This was an observational study carried out in a tertiary referral cancer hospital. Two hundred seventy four patients were recruited to the study. All had a diagnosis of cancer and were on oral morphine for cancer pain. The main outcomes measured were subjective patient assessment of constipation severity in the preceding week and laxative use. Patients were asked to grade constipation in the preceding week on a four-point categorical scale: "not at all" (grade 0), "a little" (grade 1), "quite a bit" (grade 2) and "very much" (grade 3). Laxative dose groups (LDGs) were developed to assess laxative dosing. RESULTS: Constipation affects 72% of this cohort of patients. Constipation in this population is poorly managed. Eighty nine percent of constipated patients were on inadequate laxative therapy. Inter-individual variation in constipation on morphine exists: some patients do not experience constipation and do not need to take any laxatives, some patients do not experience constipation because they are taking laxatives and some patients experience constipation despite being on high dose laxatives. These three groups were compared in terms of cancer diagnosis, time on morphine, dose of morphine and other concomitant factors. No factor was identified to account for this inter-individual variation. Improvement in the clinical management of constipation is needed, with titration of laxatives according to individual patient need. CONCLUSION: Constipation affects a large proportion of cancer patients taking oral morphine. Constipation in these patients is generally inadequately treated.

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Eur J Gastroenterol Hepatol. 2008 Jan;20(1):56-61.
Constipation during pregnancy: a longitudinal survey based on self-reported symptoms and the Rome II criteria.
Ponce J, Martínez B, Fernández A, Ponce M, Bastida G, Plá E, Garrigues V, Ortiz V.
Gastroenterology Unit, Hospital Universitari La Fe, Valencia, Spain. jponceg@medynet.com

An increase in the prevalence of constipation during pregnancy has been suggested to occur. We designed a prospective study to evaluate the prevalence of constipation during pregnancy and puerperium, to investigate possible associations with eating habits and lifestyle, and to evaluate the frequency of laxative use. A structured questionnaire was developed addressing demographics, obstetric characteristics, lifestyle, eating habits, variables required for the diagnosis of constipation, and laxative use to evaluate the prevalence of constipation during pregnancy and puerperium. The questionnaire was administered in the obstetric clinic in the first trimester of pregnancy, and by telephone in the second and third trimesters, and in the puerperal period. The prevalence of self-reported constipation in these time periods was 45.4, 37.1, 39.4, and 41.8%, respectively. Prevalence defined by the Rome II criteria for the same time periods was 29.6, 19, 21.8, and 24.7%. These values were similar to the data previously reported for the female population. Agreement between the self-reported and Rome II results was moderate. The self-reported criterion showed high sensitivity in all time periods, using the Rome II criterion as gold-standard. No factor was associated with variations in the prevalence of constipation during pregnancy, though an increase was recorded in the consumption of fruit, vegetables, fiber, and water. The prevalence of constipation during pregnancy and puerperium is similar to that recorded among the female population from the same geographic area.

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Obstet Gynecol. 2007 Dec;110(6):1351-7.
Constipation in pregnancy: prevalence, symptoms, and risk factors.
Bradley CS, Kennedy CM, Turcea AM, Rao SS, Nygaard IE.
Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. catherine-bradley@uiowa.edu

OBJECTIVE: To prospectively estimate constipation prevalence and risk factors in pregnancy. METHODS: We enrolled healthy pregnant women in this longitudinal study during the first trimester. At each trimester and 3 months postpartum, participants completed a self-administered bowel symptom questionnaire, physical activity and dietary fiber intake measures, and a prospective 7-day stool diary. Constipation was defined using the Rome II criteria (presence of at least two of the following symptoms for at least one quarter of defecations: straining, lumpy or hard stools, sensation of incomplete evacuation, sensation of anorectal obstruction, manual maneuvers to facilitate defecation, and fewer than three defecations per week). Generalized linear logistic models explored factors associated with constipation during pregnancy. RESULTS: One hundred three women were enrolled with mean (+/-standard deviation) age of 28 (+/-5) years; 54% were nulliparous and 92% white. Constipation prevalence rates were 24% (95% confidence interval [CI] 16-33%), 26% (95% CI 17-38%), 16% (95% CI 8-26%), and 24% (95% CI 13-36%) in the first, second, and third trimesters and 3 months postpartum, respectively. Additionally, irritable bowel syndrome (by Rome II criteria) prevalence rates were 19% (95% CI 12-28%), 13% (95% CI 6-23%), 13% (95% CI 6-23%) and 5% (95% CI 1-13%) in the first, second, and third trimesters and 3 months postpartum, respectively. In multivariable longitudinal analysis, iron supplements (OR 3.5, 95% CI 1.04-12.10) and past constipation treatment (OR 3.58, 95% CI 1.50-8.57) were associated with constipation during pregnancy. CONCLUSION: Constipation measured using the Rome II criteria affects up to one fourth of women throughout pregnancy and at 3 months postpartum. LEVEL OF EVIDENCE: II.

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Aliment Pharmacol Ther. 2007 Dec;26 Suppl 2:133-48.
Review article: Probiotics in gastrointestinal and liver diseases.
Jonkers D, Stockbrügger R.
Div. Gastroenterology-Hepatology, University Hospital Maastricht, Maastricht, The Netherlands. d.jonkers@intmed.unimaas.nl

BACKGROUND: Probiotics, defined as live micro-organisms with beneficial effects for the host, are widely applied in gastrointestinal and liver diseases. AIM AND METHOD: To review the available evidence of clinical trials on probiotics in gastrointestinal and liver diseases, with a major focus on irritable bowel syndrome, inflammatory bowel disease, pancreatitis and chronic liver diseases. RESULTS: Evidence for the therapeutic or preventive application of particular probiotic strains is available for antibiotic-associated diarrhoea, rota-virus-associated diarrhoea and pouchitis. Results are encouraging for irritable bowel syndrome, ulcerative colitis and for reducing side effects by Helicobacter pylori eradication therapies, but are less clear for Crohn's disease, lactose intolerance and constipation. In general, for most of these patient groups, more placebo-controlled methodologically well-designed studies that pay attention to both clinical outcome and mechanistic aspects are required. The application in liver disease and pancreatitis is promising, but more human trials have to be awaited. Possible mechanisms of probiotics include modulation of the intestinal microbiota and the immune system, but different bacterial may have different effects. CONCLUSION: Further insight into disease entities and the functioning of probiotic strains is required to be able to select disease-specific strains, which have to be tested in well-designed placebo-controlled studies.

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Dis Colon Rectum. 2007 Dec 22 [Epub ahead of print]
Results, Outcome Predictors, and Complications after Stapled Transanal Rectal Resection for Obstructed Defecation.
Gagliardi G, Pescatori M, Altomare DF, Binda GA, Bottini C, Dodi G, Filingeri V, Milito G, Rinaldi M, Romano G, Spazzafumo L, Trompetto M; on behalf of the Italian Society of Colo-Rectal Surgery (SICCR).
General Surgery, Clinica Pineta Grande, Via Domiziana Km. 30, Castel Volturno (Caserta), 81030, Italy, gagliarg@yahoo.com.

PURPOSE: Obstructed defecation may be treated by stapled transanal rectal resection, but different complications and recurrence rates have been reported. The present study was designed to evaluate stapled transanal rectal resection results, outcome predictive factors, and nature of complications. METHODS: Clinical and functional data of 123 patients were retrospectively analyzed. All patients had symptoms of obstructed defecation before surgery and had rectocele and/or intussusception. Of them, 85 were operated on by the authors and 38 were referred after stapled transanal rectal resection had been performed elsewhere. RESULTS: At a median follow-up of 17 (range, 3-44) months, 65 percent of the patients operated on by the authors had subjective improvement. Recurrent rectocele was present in 29 percent and recurrent intussusception was present in 28 percent of patients. At univariate analysis, results were worse in those with preoperative digitation (P < 0.01), puborectalis d
yssynergia (P < 0.05), enterocele (P < 0.05), larger size rectocele (P < 0.05), lower bowel frequency (P < 0.05), and sense of incomplete evacuation (P < 0.05). Bleeding was the most common perioperative complication occurring in 12 percent of cases. Reoperations were needed in 16 patients (19 percent): 9 for recurrent disease. In the 38 patients referred after stapled transanal rectal resection, the most common problems were perineal pain (53 percent), constipation with recurrent rectocele and/or intussusception (50 percent), and incontinence (28 percent). Of these patients, 14 (37 percent) underwent reoperations: 7 for recurrence. Three patients presented with a rectovaginal fistula. One other patient died for necrotizing pelvic fasciitis. CONCLUSIONS: Stapled transanal rectal resection achieved acceptable results at the cost of a high reoperation rate. Patients with puborectalis dyssynergia and lower bowel frequency may do worse because surgery does not address the causes of their constipation. Patients with large rectoceles, enteroceles, digitation, and a sense of incomplete evacuation may have more advanced pelvic floor disease for which stapled transanal rectal resection, which simply removes redundant tissue, may not be adequate. This, together with the complications observed in patients referred after stapled transanal rectal resection, suggests that this procedure should be performed by colorectal surgeons and in carefully selected patients.

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Rev Gastroenterol Disord. 2007 Fall;7(4):214-22.
Lubiprostone: a new drug for the treatment of chronic idiopathic constipation.
Baker DE.
College of Pharmacy, Washington State University Spokane, Spokane, Washington, USA.

Lubiprostone offers an additional alternative for patients with chronic idiopathic constipation. Lubiprostone is more efficacious than placebo in the treatment of chronic idiopathic constipation. In placebo-controlled clinical trials, lubiprostone therapy was generally well tolerated and was not associated with severe adverse effects; however, the high incidence of nausea may be problematic for some patients. The nausea may be alleviated or minimized by administering the dose with food, and some patients may require a dosage reduction to 24 mug once daily. The key limitations of the placebo-controlled clinical trials include the absence of information regarding the duration of the constipation and previous types of therapies that had been used to treat the constipation and the absence of an active control group. Comparative studies with other therapies (eg, saline laxatives, polyethylene glycol) used for constipation are necessary to determine the clinical and economic value of this agent relative to other forms of therapy.

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MMW Fortschr Med. 2007 Nov 1;149(44):39-42.
[Constipation in patients with diabetes mellitus]
[Article in German]
Rossol S.
Medizinische Klinik, Krankenhaus Nordwest, Frankfurt am Main. siegbert.rossol@khnwo.de

Up to 60% of the patients with diabetes mellitus suffer from gastrointestinal tract symptoms that arise pathogenetically from a disturbance of the autonomous nervous system. Patient age, disease duration and poor control of diabetes mellitus correlate positively with the presence of gastrointestinal symptoms. Chronic constipation, in addition to diarrhoea, gall bladder dysfunction and incontinence, is increasingly regarded as a serious problem and for the first time, is now considered in the current guidelines of the professional societies. Modern diagnosis and treatment facilitate systematic control of the symptoms. Treatment necessitates long-term intake of laxatives, proper diabetes control and other accompanying general measures such as adequate amounts of liquids, dietary fibre and exercise. Motility and secretion-stimulating, osmotically active or locally applied laxatives are used. Slow transit constipation, which is typically observed in diabetics, can be best controlled with polyethylene glycol, bisacodyl or sodium picosulphate.

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J Urol. 2007 Nov 13; [Epub ahead of print]
Intermediate-Term Outcome of the Simplified Laparoscopic Antegrade Continence Enema Procedure: Less is Better.
Nanigian DK, Kurzrock EA.
Department of Urology, Children's Hospital, University of California Davis School of Medicine and Shriner's Hospitals for Children-Northern California, Sacramento, California.

PURPOSE: The Malone antegrade continence enema procedure revolutionized the surgical management of fecal incontinence. Open and laparoscopic antegrade continence enemas are often performed with cecoplication and mesenteric manipulation. Since our initial laparoscopic antegrade continence enema description, we have simplified our technique. We present our series of laparoscopic antegrade continence enema procedures, discuss technique and outcomes, and review the literature. MATERIALS AND METHODS: We retrospectively reviewed children who underwent laparoscopic antegrade continence enema between 2001 and 2007. Outcome measures included operative time, length of stay, stomal complications and resolution of incontinence or constipation. Using an umbilical port and 1 to 2 additional ports, the appendix was mobilized to allow transposition to the umbilicus. No cecoplication was performed. The appendix was not straightened unless catheterization was difficult. RESULTS: A total of 22 patients (mean age 7.8 years) underwent laparoscopic antegrade continence enema. Of the patients 21 were discharged home on postoperative day 1. Mean operative time was 65 minutes (range 30 to 116). In the last 10 patients only 1 working port was used. No perioperative complications were encountered. Mean followup was 24 months (range 1 to 68). Constipation and fecal incontinence resolved in all cases. No patient experienced stomal complications. One obese patient with kyphosis could not pass the catheter beyond the mid appendix at 1 month postoperatively. She had the same problem 1 month following open antegrade continence enema with cecoplication. CONCLUSIONS: Laparoscopic antegrade continence enema is an effective means of treating intractable fecal incontinence and constipation. Our technique of using in situ appendix without cecoplication requires minimal mobilization and manipulation of the blood supply. Secondary ischemia, adhesions and scar formation are reduced, alleviating the most common complication, stomal stenosis. Our results show that cecoplication is not necessary to maintain stomal continence.

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South Med J. 2007 Nov;100(11):1085-90.
A comparison of polyethylene glycol laxative and placebo for relief of constipation from constipating medications.
Dipalma JA, Cleveland MB, McGowan J, Herrera JL.
From the Division of Gastroenterology, University of South Alabama College of Medicine, Mobile, Alabama, and Braintree Laboratories, Inc., Braintree, Massachusetts.

OBJECTIVES:: Medications often cause constipation and little data are available concerning treatment interventions. This study was designed to evaluate the safety and efficacy of polyethylene glycol (PEG) 3350 laxative (MiraLax) for relief of constipation from medicines associated with symptoms of constipation. METHODS:: Study subjects were enrolled who met defined criteria for chronic constipation and were also taking medications that were associated with a reported side effect incidence of more than 3% constipation. Subjects were randomized into a double-blind, parallel, multicenter study where they received 17 g per day of PEG laxative or placebo for 28 days. The primary efficacy variable, "Treatment Success," was defined as relief of ROME II criteria for constipation over the last 7 days of the treatment period. Various secondary measures were also assessed. Daily bowel movement experience, patient perception of efficacy, and safety information were recorded in a diary. Laboratory testing was performed at baseline and at end of study for hematology and blood chemistry, including BUN, calcium, electrolytes, and TSH. RESULTS:: One hundred patients were enrolled at 4 study centers. Successful treatment according to the primary efficacy variable was seen in 78.3% of PEG and 39.1% of placebo subjects (P < 0.001). Similar results were observed in a subgroup of 28 elderly subjects. Secondary measures of number of bowel movements, complete bowel movements, satisfactory bowel movements, straining at stool and stool consistency also showed statistically significant results in favor of PEG compared with placebo (P </= 0.01) after the first week of treatment. There were no differences inpatient reported scores for gas, cramping, or bloating between PEG and placebo. No significant differences in laboratory findings or adverse events, including the gastrointestinal category, were observed. Diarrhea and flatulence occurred more frequently with PEG treatment, although they were not individually statistically different from placebo. Similar results were observed when these symptoms were analyzed for differences due to gender, race, or age. CONCLUSIONS:: PEG laxative is safe and effective for use in treating constipation in patients taking constipating medications.

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Am J Gastroenterol. 2007 Oct 4; [Epub ahead of print]
Multicenter, 4-Week, Double-Blind, Randomized, Placebo-Controlled Trial of Lubiprostone, a Locally-Acting Type-2 Chloride Channel Activator, in Patients With Chronic Constipation.
Johanson JF, Morton D, Geenen J, Ueno R.
University of Illinois College of Medicine, Rockford, Illinois, USA.

OBJECTIVES: To assess the efficacy and safety of lubiprostone in adults with chronic constipation. METHODS: This multicenter, parallel-group, double-blind controlled trial enrolled 242 patients with constipation and randomized them to receive oral lubiprostone 24 mcg or placebo twice daily for 4 wk. The primary efficacy end point was the number of spontaneous bowel movements (SBMs; those occurring without use of constipation relieving medications) after 1 wk of double-blind treatment. Other evaluations included SBMs at weeks 2, 3, and 4; bowel movement (BM) characteristics (i.e., consistency and straining); constipation severity; abdominal bloating/discomfort; global treatment effectiveness ratings; and safety assessments. RESULTS: The 120 lubiprostone-treated patients reported a greater mean number of SBMs at week 1 compared with the 122 placebo-treated patients (5.69 vs 3.46, P= 0.0001), with a greater frequency of SBMs also reported at weeks 2, 3, and 4 (P</= 0.002). Within 24 h of the first dose of study drug, 56.7% of those given lubiprostone reported a SBM compared with 36.9% of those given placebo (P= 0.0024); within 48 h, 80% and 60.7% of these patients reported a SBM (P= 0.0013), respectively. Stool consistency, straining, and constipation severity, as well as patient-reported assessments of treatment effectiveness, were significantly improved with lubiprostone compared with placebo at all weeks (P</= 0.0003). The two most common treatment-related adverse events were nausea (31.7%) and headache (11.7%). CONCLUSIONS: In patients with chronic constipation, treatment with lubiprostone produces a BM in the majority of individuals within 24-48 h of initial dosing and improves the frequency as well as other characteristics associated with BMs with short-term (i.e., 4 wk) treatment. The most commonly reported adverse event was mild to moderate nausea, which resulted in treatment discontinuation in 5% of treated patients.

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Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003960.
Tegaserod for the treatment of irritable bowel syndrome and chronic constipation.
Evans B, Clark W, Moore Dj, Whorwell P.

BACKGROUND: IBS is a complex disorder that encompasses a wide profile of symptoms. The symptoms of chronic constipation frequently resemble those of constipation-predominant IBS. Current drug treatments for irritable bowel syndrome (IBS) are of limited value. Many target specific symptoms only. Tegaserod, a 5HT(4) partial agonist, represents a novel mechanism of action in the treatment of IBS and chronic constipation. OBJECTIVES: The objective of this review was to evaluate the efficacy and tolerability of tegaserod for the treatment of IBS and chronic constipation in adults and adolescents aged 12 years and above. SEARCH STRATEGY: MEDLINE 1966-December 2006 and EMBASE 1980 to December 2006 were searched. The text and key words used included "tegaserod", "HTF 919", "irritable bowel", "constipation" and "colonic diseases, functional". The Cochrane Central Register of Controlled Trials, and the Inflammatory Bowel Disease Review Group Specialized Trials Register were also searched. Searches stopped on 15th December 2006. Relevant articles were retrieved, and their reference lists were also reviewed. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing tegaserod with placebo, no treatment or any other intervention (pharmacological or non-pharmacological) in subjects aged 12 years and above with a diagnosis of IBS or chronic constipation, focusing on clinical endpoints were considered for review. DATA COLLECTION AND ANALYSIS: Study inclusion and exclusion, data extraction and quality assessment was undertaken by two authors independently. Meta-analysis was performed where study populations, designs, outcomes, and statistical reporting allowed combination of data in a valid way, using the summary statistics relative risk for dichotomous data and weighted mean difference for continuous data, both with 95% CI. Thirteen short-term placebo-controlled studies fulfilled the inclusion criteria. These were predominantly conducted in women. Ten studies evaluated the efficacy of tegaserod on global gastrointestinal (GI) symptoms in patients with constipation-predominant IBS (C-IBS). One small study evaluated safety in patients with diarrhoea-predominant IBS. Two studies evaluated the effectiveness of tegaserod for the treatment of chronic constipation. MAIN RESULTS: In patients with C-IBS, the relative risk (RR) of being a responder in terms of global relief of GI symptoms during the last 4 weeks of treatment was significantly higher with both tegaserod 12 mg and 4 mg doses compared with placebo. Although the pooled results indicate statistically significant benefit with tegaserod, the a priori minimal clinically important differences set in two of three studies were not reached. The responder rate for this endpoint was also higher when considered for the first 4 weeks of treatment (tegaserod 12 mg only). Tegaserod did not significantly improve the patients' individual symptoms of abdominal pain and discomfort although bowel habit showed a statistically significant improvement with tegaserod 4 mg and there was a non-significant trend in this outcome in favour of tegaserod 12 mg. In patients with chronic constipation, the RR of being a responder in terms of complete spontaneous bowel movements per week with tegaserod 12 mg was 1.54 (95% CI 1.35 to 1.75), WMD for this endpoint compared with placebo 0.6 (95% CI 0.42 to 0.78). Differences between tegaserod and placebo in increases in frequency of bowel movements were small (less than one per week). The proportion of patients with either diagnosis who experienced diarrhea was significantly higher in the tegaserod 12 mg group compared with placebo (RR 2.80, 95% CI 2.13 to 3.68), with a number needed to harm (NNH) of 20. Effects of tegaserod on GI symptoms such as bloating, stool consistency, and straining were not consistent across the studies. AUTHORS' CONCLUSIONS: Tegaserod appears to improve the overall symptomatology of IBS, and the frequency of bowel movements in those with chronic constipation. The clinical importance of these modest improvements is not clear. There are currently few data on its effect on quality of life. In addition, more information is needed about its efficacy in men. It would also be of interest to know whether treatment with tegaserod leads either directly, or indirectly, to changes in visceral sensitivity or psychopathology, which are also considered important in the pathophysiology of these conditions.

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Gastroenterol Clin North Am. 2007 Sep;36(3):713-34.
Gastrointestinal electrical stimulation for treatment of gastrointestinal disorders: gastroparesis, obesity, fecal incontinence, and constipation.
Lin Z, Sarosiek I, McCallum RW.
Center for GI Nerve and Muscle Function, Department of Internal Medicine, University of Kansas Medical Center, Mail Stop 1058, 3910 Rainbow Boulevard, Kansas City, KS 66160, USA.

Electrical stimulation of the gastrointestinal (GI) tract is an attractive concept. Since these organs have their own natural pacemakers, the electrical signals they generate can be altered by externally delivering electric currents by intramuscular, serosal, or intraluminal electrodes to specific sites in the GI tract. This article reviews the advances in electrical stimulation of the GI tract by describing various methods of GI electrical stimulation and their peripheral and central effects and mechanisms; updating the status of GI electrical stimulation in the clinical settings of gastroparesis, obesity, fecal incontinence, and constipation; and predicting future directions and developments of GI electrical stimulation technology and their areas of possible clinical applications.

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Urology. 2007 Sep;70(3):568-71.
Minimally invasive approach for treatment of urinary and fecal incontinence in selected patients with spina bifida.
Lorenzo AJ, Chait PG, Wallis MC, Raikhlin A, Farhat WA.
Division of Urology and Department of Diagnostic Imaging, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.

OBJECTIVES: At our institution, the use of cecostomy tubes has provided a successful method for managing severe constipation in patients with spina bifida, with good patient and caretaker satisfaction and minimal morbidity. We have developed a modified technique to allow placement of the cecostomy tube under direct vision during laparoscopic appendicovesicostomy. We present our initial experience and technique. METHODS: Patients with a normal bladder capacity and compliance who were scheduled for creation of an appendicovesicostomy and who also had refractory constipation were offered concurrent cecostomy tube placement. At the laparoscopic procedure, we performed percutaneous placement of the cecostomy tube through the abdominal wall under direct visualization. Subsequently, dissection of the appendix with its mesentery was performed. The detrusor muscle was dissected and a trough for the appendix created. Laparoscopic anastomosis of the appendix to the bladder mucosa and approximation of the detrusor over the appendix created a nonrefluxing channel. RESULTS: Three patients have undergone concurrent cecostomy tube placement at appendicovesicostomy. No complications have been encountered thus far. On follow-up, the cecostomy tube scar has been well concealed and appears no different from the ones placed under radiologic guidance. The patients have been using the catheterizable channel to access the bladder and dry performing intermittent catheterization without difficulties. CONCLUSIONS: In patients with a neurogenic bladder who do not qualify for major bladder reconstructive procedures, such as augmentation cystoplasty or bladder neck repair, social continence and independence can be achieved with minimally invasive surgery. Concomitant laparoscopic appendicovesicostomy and cecostomy tube placement may be a suitable surgical option.

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Rev Gastroenterol Disord. 2007 Summer;7(3):116-33.
Fresh perspectives in chronic constipation and other functional bowel disorders.
Cash BD, Chang E, Talley NJ, Wald A.
Gastroenterology Division and Colon Health Initiative, National Naval Medical Center, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.

Functional bowel disorders (FBDs) such as chronic constipation and irritable bowel syndrome-constipation predominant (IBS-C) often share symptoms, but thanks to advances such as the Rome III criteria, diagnosis of these conditions in the absence of alarm features can be relatively straightforward. Empiric treatment is recommended for most patients, with diagnostic testing reserved for those with alarm symptoms. Most current therapies for constipation are indicated for patients with occasional symptoms, with only lubiprostone and tegaserod (restricted) indicated for chronic constipation. Therapies for IBS-C also are limited. However, ongoing research provides promise for improved outcomes in patients with FBDs.

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Ann Pharmacother. 2007 Jun;41(6):957-64. Epub 2007 May 22.
Lubiprostone: a chloride channel activator for treatment of chronic constipation.
Ambizas EM, Ginzburg R.
College of Pharmacy & Allied Health Professions, St John's University, Queens, NY 11439, USA. arweilee@stjohns.edu

OBJECTIVE: To review lubiprostone's pharmacology, pharmacokinetics, efficacy, and safety in the treatment of chronic constipation. DATA SOURCES: A literature search was conducted using PubMed/MEDLINE (1966-January 2007), IngentaConnect, and International Pharmaceutical Abstracts (1977-January 2007). Key words used included lubiprostone, Amitiza, and chronic constipation. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources that were published in English were evaluated. DATA SYNTHESIS: Lubiprostone is a chloride channel activator approved by the Food and Drug Administration for the treatment of chronic constipation. A randomized, double-blind, parallel-group, placebo-controlled study evaluating the effect of lubiprostone on gastric function showed slowed gastric emptying and increased small bowel and colonic transit time. Peak plasma concentration was shown to be around 1.14 hours, with a majority of the drug excreted in the urine within 48 hours. Phase III trials have noted that most patients with chronic constipation have a spontaneous bowel movement within 24 hours after taking lubiprostone. The most common adverse events in these trials were nausea, diarrhea, abdominal pain, and headache. Lubiprostone use has not been studied in the pediatric population. CONCLUSIONS: Lubiprostone may be a reasonable alternative for use in patients who either fail or are intolerant of standard therapy for chronic constipation. Head-to-head comparison studies with conventional therapy are needed to contrast clinical efficacy and safety of this medication.

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Curr Gastroenterol Rep. 2007 Jun;9(3):214-8.
Novel and alternative therapies for childhood constipation.
Liem O, Benninga MA, Mousa HM, Di Lorenzo C.
Department of Pediatric Gastroenterology and Nutrition, Columbus Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA. liemo@chi.osu.edu

Constipation is a worldwide problem that affects many children. Treatment of constipation is largely based on clinical experience rather than on evidence-based controlled clinical trials. Stool softeners and cathartic agents in combination with behavioral interventions constitute the programs most commonly used to facilitate painless and frequent defecation. Long-term treatment is needed for most patients, and approximately 30% of children beyond puberty continue to struggle with symptoms of constipation, such as infrequent, painful evacuation of stools and fecal incontinence. Not surprisingly, chronicity of these bowel complaints may cause significant interference with the child's emotional growth and development. Development of new therapeutic strategies is necessary in order to treat these challenging patients more effectively. This review provides an overview of novel and alternative therapies, such as new drugs, surgery, and probiotics, that are being proposed for the treatment of childhood chronic constipation.

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Aliment Pharmacol Ther. 2007 Jun 1;25(11):1351-61.
Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety.
Johanson JF, Ueno R.
Rockford Gastroenterology Associates, Rockford, IL, USA. johnfj@uic.edu

BACKGROUND: Lubiprostone, a locally acting type-2 chloride channel activator, induces intestinal fluid secretion. AIM: To assess efficacy and safety of oral lubiprostone at multiple doses for the treatment of chronic constipation. METHODS: A total of 129 patients with chronic constipation were randomized to receive lubiprostone (24, 48 or 72 mcg/day) or placebo for 3 weeks. Spontaneous bowel movement (SBM) frequency, rescue medication use, symptom assessments and adverse events (AEs) were tracked. RESULTS: Over the double-blinded period, mean SBM frequencies were higher for lubiprostone groups (5.1-6.1) vs. placebo (3.8) and the overall difference was statistically significant (P = 0.046). SBM frequencies at week 1 were significantly higher in patients taking lubiprostone 48 or 72 mcg/day (P < or = 0.003) and, at week 2, all three lubiprostone doses yielded significantly higher SBM rates vs. placebo (P < or = 0.020). Significantly larger proportions of patients taking lubiprostone 48 and 72 mcg/day also experienced a SBM on the first treatment day (P < or = 0.009). The most common AEs were nausea, headache and diarrhoea. CONCLUSIONS: Lubiprostone improved SBM rates in a dose-dependent manner. AEs were tolerable for most patients. Increased AE severity at 72 mcg/day did not provide a clear risk-to-benefit advantage compared with lubiprostone 48 mcg/day, the dose chosen for subsequent Phase 3 studies.

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Int J Clin Pract. 2007 Jun;61(6):944-50.
Randomised, placebo-controlled, double-blind study to investigate the efficacy and safety of the acute use of sodium picosulphate in patients with chronic constipation.
Wulkow R, Vix JM, Schuijt C, Peil H, Kamm MA, Jordan C.
Quintiles GmbH, Freiburg, Germany.

There are few studies supporting the effective and safe use of laxatives for constipation. This study examined the short-term efficacy and safety of sodium picosulphate in patients with chronic constipation. Patients with a history of chronic constipation for at least 3 months were randomised to receive 7 mg sodium picosulphate or placebo for three consecutive nights. Patients recorded stool frequency and consistency, straining, bloating, and pain at baseline and during treatment. Vital signs, haematocrit, serum creatinine and electrolytes were monitored. Primary end-point for efficacy was the occurrence of a response to treatment, defined as improvement in stool frequency and occurrence of straining. All 57 randomised patients (sodium picosulphate n = 29, placebo n = 28; mean age 54.8 and 54.1 years) completed the study. Sodium picosulphate produced a treatment response (improved stool frequency and straining) in 82.8% compared with 50% in the placebo group (p = 0.010) and reduced bloating more often than placebo. There were no serious adverse events and one patient with diarrhoea and another with abdominal pain in each treatment group. There were no cardiovascular effects, changes in serum haematocrit, creatinine or electrolytes in either group. This study confirmed that sodium picosulphate is an effective, well-tolerated and safe laxative in the acute treatment of constipation.

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World J Surg. 2007 May 31; [Epub ahead of print]
Subtotal Colectomy with Antiperistaltic Cecorectal Anastomosis in the Treatment of Slow-transit Constipation: Long-term Impact on Quality of Life.
Marchesi F, Sarli L, Percalli L, Sansebastiano GE, Veronesi L, Mauro DD, Porrini C, Ferro M, Roncoroni L.
Department of Surgical Sciences, Section of General Surgical Clinics and Surgical Therapy, Parma University Medical School, Parma, Italy, fede53@lycos.com.

BACKGROUND: The aim of the study was to evaluate the effectiveness of subtotal colectomy with cecorectal anastomosis (SCCA) in the treatment of slow-transit constipation, not just in terms of symptom resolution but also the overall impact on patients' quality of life. METHODS: Between 1991 and 2005, 43 patients underwent SCCA at our institution, 22 for slow-transit constipation (STC) and 21 for other types of colic diffuse disease (non-slow-transit constipation: NSTC), the latter being considered controls. A total of 29 patients (17 affected by STC) were administered a 50-item telephonic questionnaire, including the Gastrointestinal Quality of Life Index (GIQLI), the Wexner constipation and incontinence scale (WC, WI), and individual willingness to repeat the procedure. Questionnaire data and other parameters such as age, sex, length of follow-up, complications, and length of hospital stay were analyzed and compared, in order to evaluate possible correlations between the parameters and their related impact on quality of life, procedural effectiveness in terms of symptomatic regression, qualitative differences related to pathology (constipation versus non-constipation), and surgical approach (laparotomy versus video-laparo-assisted procedure). RESULTS: There were no procedure-related deaths in this series (mortality: 0%); however, we found two complications in the STC group (9.1%), one requiring reoperation. The GIQLI mean score for the STC group was 115.5 +/- 20.5 (mean score for healthy people 125.8 +/- 13), and the WC mean score passed from a preoperative value of 20.3 to a postoperative value of 2.6. Regression analysis revealed a significant correlation between GIQLI and urgency and abdominal pain, and abdominal pain correlated significantly with pathology (STC). A high number of patients (88.2% in STC) expressed a willingness to repeat the procedure given the same preoperative conditions. CONCLUSIONS: Comparing our results to those of the most homogeneous literature data, SCCA does not appear to be inferior to subtotal colectomy with ileorectal anastomosis (IRA) in terms of therapeutic effectiveness, postoperative mortality and morbidity, or overall impact on quality of life.

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J Am Med Dir Assoc. 2007 May;8(4):209-18.
Constipation in long-term care.
Tariq SH.
Division of Geriatric Medicine, Saint Louis University, St Louis, MO 63104, USA. Tariqsh@slu.edu

Constipation is more common in older adults and accounts for increased physician office visits and hospital admissions. There is lack of agreement on the definition of constipation regarding what patients perceive as constipation and what physicians traditionally see as constipation. Constipation is related to multiple factors, and when left untreated or not properly treated, results in complications, such as impaction, even perforation and death. Laxative use increases with age and at times multiple agents are used to relieve symptoms of constipation. Currently the most commonly used laxative is stool softener but it lacks efficacy. From the review of literature, osmotic laxatives are effective in older adults and well tolerated. Psyllium, a bulk laxative, is also effective in the treatment of constipation, while there is limited evidence for stimulants, dioctyl sulfosuccinate, and other bulk laxatives such as calcium polycarbophil and methylcellulose. A new drug, lubiprostone, is a type 2-chloride channel activator and is shown to be effective, safe, and well tolerated in older adults treated for chronic constipation in studies up to a year. It appears to be particularly useful in persons who have recurrent fecal impaction and in those with severe chronic constipation. There is a need for a large-scale trial examining an appropriate cost-effective approach to the management of constipation in the nursing home.

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ANZ J Surg. 2007 May;77(5):320-8.
Slow-transit constipation: evaluation and treatment.
Wong SW, Lubowski DZ.
Department of Surgery, Prince of Wales Hospital, Sydney, NSW, Australia.

Slow-transit constipation is characterized by delay in transit of stool through the colon, caused by either myopathy or neuropathy. The severity of constipation is highly variable, but may be severe enough to result in complete cessation of spontaneous bowel motions. Diagnostic tests to assess colonic transit include radiopaque marker or radioisotope studies, and intraluminal tests (colonic and small bowel manometry). Most patients with functional constipation respond to laxatives, but a small proportion are resistant to this treatment. In some patients biofeedback is helpful although the mechanism by which this works is still uncertain. Other patients are resistant to all conservative modes of therapy and require surgical intervention. Extensive clinical and physiological preoperative assessment of patients with slow colonic transit is essential before considering surgery, including an assessment of small bowel motility and identification of coexistent obstructed defecation. The psychological state of the patient should always be taken into account. When surgery is indicated, subtotal colectomy and ileorectal anastomosis is the operation of choice. Segmental colonic resection has been reported in a few patients, but methods of identifying the affected segment need to be developed further. Less invasive and reversible surgical options include laparoscopic ileostomy, antegrade colonic enema and sacral nerve stimulation.

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Eur J Clin Nutr. 2007 Feb 14; [Epub ahead of print]
Yogurt containing galacto-oligosaccharides, prunes and linseed reduces the severity of mild constipation in elderly subjects.
Sairanen U, Piirainen L, Nevala R, Korpela R.
1Valio Ltd R&#38;D, Helsinki, Finland.

Objective:Constipation is a common problem in the elderly. Dietary fibre is recommended for its treatment. The aim was to examine whether yoghurt containing galacto-oligosaccharides (GOS), prunes and linseed relieve constipation in elderly subjects.Design:A randomized, double-blinded, cross-over study.Setting:Free-living subjects.Subjects:A group of 43 elderly subjects with self-reported constipation (mean age 76 years, range 61-92 years, 32 females, 11 males).Interventions:The study consisted of a 2-week baseline period and 2, 3-week dietary interventions, with a 2-week wash-out period between the interventions. During the interventions, the subjects ingested, in random order, 260 g/day of either control yoghurt or test yoghurt containing GOS (12 g/day), prunes (12 g/day) and linseed (6 g/day). The use of laxatives was controlled and only allowed after 2 days without defecation.Results:Defecation frequency was 5.7 times/week during the baseline period. During the test yoghurt period, defecation frequency was higher (8.0 vs 7.1 times/week, P=0.011), defecation was easier (on the scale 0-3, 1.3 vs 1.5, P=0.010), and there was a tendency towards softer stools (on the scale 0-3, 2.1 vs 2.2, P=0.059) compared with the control yoghurt period. The subjects felt that the test yoghurt relieved constipation more effectively than the control yoghurt (P=0.005). The sum of gastrointestinal symptoms did not differ between the interventions. The use of laxatives remained constant throughout the study.Conclusions:Daily intake of yoghurt containing GOS, prunes and linseed reduced the severity of constipation in elderly subjects with mild constipation.Sponsorship:Valio Ltd, R&#38;D.European Journal of Clinical Nutrition advance online publication, 14 February 2007; doi:10.1038/sj.ejcn.1602670.

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Dis Colon Rectum. 2007 Feb 7; [Epub ahead of print]
Randomized, Controlled Trial Shows Biofeedback to be Superior to Alternative Treatments for Patients with Pelvic Floor Dyssynergia-Type Constipation.
Heymen S, Scarlett Y, Jones K, Ringel Y, Drossman D, Whitehead WE.
UNC Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA, steve_heymen@med.unc.edu.

PURPOSE: This study was designed to determine whether biofeedback is more effective than diazepam or placebo in a randomized, controlled trial for patients with pelvic floor dyssynergia-type constipation, and whether instrumented biofeedback is necessary for successful training. METHODS: A total of 117 patients participated in a four-week run-in (education and medical management). The 84 who remained constipated were randomized to biofeedback (n=30), diazepam (n=30), or placebo (n=24). All patients were trained to do pelvic floor muscle exercises to correct pelvic floor dyssynergia during six biweekly one-hour sessions, but only biofeedback patients received electromyography feedback. All other patients received pills one to two hours before attempting defecation. Diary data on cathartic use, straining, incomplete bowel movements, Bristol stool scores, and compliance with homework were reviewed biweekly. RESULTS: Before treatment, the groups did not differ on demographic (average age, 50 years; 85 percent females), physiologic or psychologic characteristics, severity of constipation, or expectation of benefit. Biofeedback was superior to diazepam by intention-to-treat analysis (70 vs. 23 percent reported adequate relief of constipation 3 months after treatment, chi-squared=13.1, P<0.001), and also superior to placebo (38 percent successful, chi-squared=5.7, P=0.017). Biofeedback patients had significantly more unassisted bowel movements at follow-up compared with placebo (P=0.005), with a trend favoring biofeedback over diazepam (P=0.067). Biofeedback patients reduced pelvic floor electromyography during straining significantly more than diazepam patients (P<0.001). CONCLUSIONS: This investigation provides definitive support for the efficacy of biofeedback for pelvic floor dyssynergia and shows that instrumented biofeedback is essential to successful treatment.

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Paediatr Drugs. 2007;9(1):33-46.
Management of chronic functional constipation in childhood.
Plunkett A, Phillips CP, Beattie RM.
Paediatric Medical Unit, Southampton General Hospital, Southampton, UK.

Chronic functional constipation is a common problem in childhood, with soiling a significant issue. The morbidity is high and the treatment is complex. There is a very poor evidence base for the drug treatments used and there are considerable differences in practice in different units.The key to successful management is early diagnosis and prompt treatment with an emphasis on holistic care with multidisciplinary support where needed. For example, the practical approach in our unit at the Southampton General Hospital, Southampton, England emphasizes the non-drug aspects including patient education and behavioral modification and uses stimulant laxatives, usually in a high dose as first-line therapy.There is an urgent need for prospective comparative studies to investigate different treatment regimens and for longitudinal studies to examine the long-term outcome of chronic constipation and the factors that determine it. The lack of a significant evidence base for the use of the most widely used agents proves a significant challenge in the production of evidence-based guidelines and highlights the paucity of data for most of the widely used treatments for childhood constipation.

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Pathologe. 2007 Feb 3; [Epub ahead of print]
[Therapeutic strategies for chronic constipation in childhood: pediatric gastroenterological and surgical aspects.]
[Article in German]
Rolle U, Till H.
Klinik und Poliklinik fur Kinderchirurgie, Universitat Leipzig, Oststrasse 21-25, 04317, Leipzig, Deutschland, rolleu@medizin.uni-leipzig.de.

Chronic constipation in childhood results from (1) psychological/behavioural causes, (2) functional or organic gastrointestinal outlet obstruction, or (3) slowing of transit within the colon. Functional chronic constipation is treated by a complex conservative bowel management. Constipation refractory to routine medical treatment reveals, in a significant number of cases, organic causes. Histology of bowel biopsies is essential for the preoperative diagnosis of chronic constipation. Defective innervated bowel segments require surgical treatment. Intraoperative histological staining of bowel biopsies allows proper resection of aganglionic or dysganglionic bowel. This contribution describes the interdisciplinary, clinicopathological interactions involving children with chronic constipation.

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Pharmacotherapy. 2007 Feb;27(2):267-77.
Tegaserod for constipation-predominant irritable bowel syndrome.
Kale-Pradhan PB, Wilhelm SM.
1 Department of Pharmacy Practice, Wayne State University, Detroit, Michigan; Department of Pharmacy, St. John Hospital and Medical Center, Detroit, Michigan.

Tegaserod, a selective and partial agonist at the 5-hydroxytryptamine (5-HT [serotonin]) receptor subtype 4 (5-HT(4)), is the only United States Food and Drug Administration-approved drug for the treatment of constipation-predominant irritable bowel syndrome (IBS) in women. The drug's stimulation of 5-HT(4) receptors on intestinal enterocytes increases peristaltic activity and fluid secretion into the gut lumen, facilitating stool passage. In addition, affinity of tegaserod for 5-HT(4) receptors modulates visceral sensitivity, which helps alleviate abdominal pain associated with constipation-predominant IBS. The drug's pharmacokinetic and pharmacodynamic parameters do not differ significantly with age or sex. Tegaserod safely and effectively relieves overall gastrointestinal symptoms and abdominal discomfort and normalizes bowel habits in patients with constipation-predominant IBS. It is associated with few drug interactions. In clinical studies, tegaserod was well tolerated, and its adverse-effect profile was similar to that of placebo. Severe diarrhea, as well as abdominal pain, flatulence, headache, and nausea, were the most commonly reported events. Patients who experience severe diarrhea should discontinue the drug. With the data available, tegaserod remains an option for patients with constipation-predominant IBS.

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Pediatr Emerg Care. 2007 Jan;23(1):1-4.
Emergency department management and short-term outcome of children with constipation.
Miller MK, Dowd MD, Fraker M.
Division of Emergency Medicine, Children's Mercy Hospital, Kansas City, MO 64108, USA. mmiller@cmh.edu

BACKGROUND: Constipation is a common diagnosis made in the pediatric emergency department (ED). Specific evidence-based standards for evaluation and treatment are lacking. OBJECTIVE: To describe variation in evaluation and treatment of constipation and characteristics and treatments associated with improvement. METHODS: This single-site descriptive study examined constipated children discharged from the ED. Chart review provided history, examination, evaluation, and treatment. Symptoms and on-going treatment were assessed by telephone interview at 4 to 6 weeks. Patients were dichotomized to poor versus adequate responders. Poor responders had 2 or more of the following: overall constipation, persistent presenting symptom, bowel movement frequency of less than once every other day, painful defecation, and/or abdominal pain. RESULTS: The study group had 121 patients, with mean age of 6.4 years; 54% were female. Abdominal pain was the most common complaint (66%); 46% reported hard/infrequent stools. Most (67%) had symptoms for less than 1 week. Many (41%) previously sought care for the same problem. Most (70%) had abdominal radiographs. One third received an enema in the ED, and most patients were prescribed laxatives, most commonly polyethylene glycol (80%). After an enema, 28% were discharged without constipation medication. At follow-up, 35% were using laxatives, and 27% had sought additional care. Nearly half (42%) were poor responders. Poor responders were younger (5.1 vs. 7.3 years; P < 0.01). There was no difference in response based upon sex, duration of symptoms, or ED treatment. CONCLUSIONS: Although older children are more likely to improve, many constipated children continue to have symptoms. Type of ED therapy is unrelated to on-going symptoms at 4 to 6 weeks.

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Curr Opin Investig Drugs. 2007 Jan;8(1):66-70.
Activation of type-2 chloride channels: a novel therapeutic target for the treatment of chronic constipation.
Crowell MD, Harris LA, DiBaise JK, Olden KW.
Mayo Clinic Scottsdale, Division of Gastroenterology and Hepatology, 13400 East Shea Blvd, Scottsdale, AZ 85259, USA. crowell.michael@mayo.edu

Chronic constipation affects up to 27% of the population and negatively impacts health-related quality-of-life. Prescription medications targeting chronic constipation currently include polyethylene glycol, lactulose and tegaserod, a serotonin type 4 receptor partial agonist. The most recent addition is lubiprostone (Amitiza), a type-2 chloride channel (ClC-2) activator which is a member of a new class of compounds known as prostones. Lubiprostone is a bicyclic fatty acid that acts locally on ClC-2 channels located in the apical membrane of intestinal epithelial cells. This stimulation of chloride secretion induces the passive movement of sodium and water into the intestinal lumen, yielding a net increase in isotonic fluid, which results in improved bowel function. In double-blind, placebo-controlled clinical trials, lubiprostone increased the number of spontaneous bowel movements compared with placebo and was generally well tolerated. The predominant adverse effects were nausea and diarrhea. Lubiprostone represents a new therapeutic class of compounds for the treatment of chronic constipation and will be the focus of this review.

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Clin Ther. 2006 Dec;28(12):2008-21.
Lubiprostone: Chloride channel activator for chronic constipation.
Rivkin A, Chagan L.

BACKGROUND:: Chronic constipation is a common and costly health problem occurring in approximately 4.5 million Americans. Current management of constipation is suboptimal and requires a stepwise approach using a combination of laxatives to decrease symptoms. OBJECTIVE:: The objective of this review was to describe the efficacy and safety of a new therapeutic entity, lubiprostone, recently approved by the US Food and Drug Administration for the treatment of chronic idiopathic constipation. METHODS:: Computerized searches of MEDLINE and International Pharmaceutical Abstracts were conducted (1966-July 10, 2006). Search terms utilized were lubiprostone, RU-0211, and chronic constipation. References of selected articles were searched for additional articles or abstracts. All relevant published literature regarding lubiprostone was included in this review. Pertinent abstracts presented at meetings of the American College of Gastroenterology and Digestive Diseases Week were also included. RESULTS:: Lubiprostone activates a chloride channel (ie, subtype 2) and increases chloride and fluid secretion into the intestines, resulting in relief of constipation. It is poorly absorbed after oral administration, and its metabolism occurs primarily in the stomach and jejunum. Lubiprostone was evaluated in 6 placebo-controlled, double-blind, randomized Phase II or III clinical trials. Overall, in clinical trials, >1400 patients were exposed to 24 mug of lubiprostone BID for up to 48 weeks. It improved the number of bowel movements, stool consistency, bloating, and global assessment of constipation compared with placebo (P < 0.05). Nausea was the most common adverse effect reported in clinical trials, occurring in 30.9% of patients. However, nausea was dose dependent and decreased when lubiprostone was given with food. CONCLUSIONS:: Lubiprostone is the first in its class of chloride channel activators that results in improvement of symptoms of constipation. It has not been compared with other laxatives but, based on the available placebo-controlled studies, its efficacy is superior to placebo and its safety is acceptable. Considering the currently available laxatives, lubiprostone will become an additional option for the treatment of patients with chronic constipation.  
 

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