Efficacy of lubiprostone for functional constipation treatment in adolescents and children: Randomized controlled trial.

OBJECTIVES: Adolescent and pediatric functional constipation (FC) is a common clinical problem. Currently, data on lubiprostone for the treatment of pediatric FC are scarce. This study investigated the efficacy and safety of lubiprostone in the treatment of pediatric FC. METHODS: In a single-blinded, randomized controlled study, we included 280 patients aged 8-18 years with FC. Patients were randomized either to a weight-based lubiprostone dose (n = 140) or conventional laxatives (n = 140), including lactulose, bisacodyl, or sodium picosulfate, for 12 weeks, followed by 4 weeks posttreatment follow-up. RESULTS: Improvement in constipation was achieved in 128 (91.4%) patients in the lubiprostone group, and in 48 (34.3%) patients of the conventional therapy group (p < 0.001) and was sustained after treatment discontinuation. One quarter of the lubiprostone group experienced the first spontaneous bowel motion within 48 h after dose initiation. A total of 75.7% of the lubiprostone group could achieve and sustain Bristol stool form of 3 or 4 during the last 4 weeks of therapy and through the 4 weeks of follow-up versus 50 (35.7%) patients in the conventional therapy group (p < 0.001). No life-threatening adverse drug reactions were encountered, and no treatment-related discontinuation. Mild self-limited colicky abdominal pain and headache were the most prevalent side effects in the lubiprostone group. CONCLUSIONS: Lubiprostone is an effective and well-tolerated pharmacotherapy for youthful age and pediatric age groups, which may alter the paradigm of pediatric FC treatment.

Clinical utility of colonic low-amplitude propagating contractions in children with functional constipation.

BACKGROUND: Colonic high-amplitude propagating contractions (HAPC) are generally accepted as a marker of neuromuscular integrity. Little is known about low-amplitude propagating contractions (LAPCs); we evaluated their clinical utility in children. METHODS: Retrospective review of children with functional constipation undergoing low-resolution colon manometry (CM) recording HAPCs and LAPCs (physiologic or bisacodyl-induced) in three groups: constipation, antegrade colonic enemas (ACE), and ileostomy. Outcome (therapy response) was compared to LAPCs in all patients and within groups. We evaluated LAPCs as potentially representing failed HAPCs. KEY RESULTS: A total of 445 patients were included (median age 9.0 years, 54% female), 73 had LAPCs. We found no association between LAPCs and outcome (all patients, p = 0.121), corroborated by logistic regression and excluding HAPCs. We found an association between physiologic LAPCs and outcome that disappears when excluding HAPCs or controlling with logistic regression. We found no association between outcome and bisacodyl-induced LAPCs or LAPC propagation. We found an association between LAPCs and outcome only in the constipation group that cancels with logistic regression and excluding HAPCs (p = 0.026, 0.062, and 0.243, respectively). We found a higher proportion of patients with LAPCs amongst those with absent or abnormally propagated (absent or partially propagated) HAPCs compared to those with fully propagated HAPCs (p = 0.001 and 0.004, respectively) suggesting LAPCs may represent failed HAPCs. CONCLUSIONS/INFERENCES: LAPCs do not seem to have added clinical significance in pediatric functional constipation; CM interpretation could rely primarily on the presence of HAPCs. LAPCs may represent failed HAPCs. Larger studies are needed to further validate these findings.

Pre-referral rectal artesunate is no "magic bullet" in weak health systems.

Severe malaria is a potentially fatal condition that requires urgent treatment. In a clinical trial, a sub-group of children treated with rectal artesunate (RAS) before being referred to a health facility had an increased chance of survival. We recently published in BMC Medicine results of the CARAMAL Project that did not find the same protective effect of pre-referral RAS implemented at scale under real-world conditions in three African countries. Instead, CARAMAL identified serious health system shortfalls that impacted the entire continuum of care, constraining the effectiveness of RAS. Correspondence to the article criticized the observational study design and the alleged interpretation and consequences of our findings.Here, we clarify that we do not dispute the life-saving potential of RAS, and discuss the methodological criticism. We acknowledge the potential for confounding in observational studies. Nevertheless, the totality of CARAMAL evidence is in full support of our conclusion that the conditions under which RAS can be beneficial were not met in our settings, as children often failed to complete referral and post-referral treatment was inadequate.The criticism did not appear to acknowledge the realities of highly malarious settings documented in detail in the CARAMAL project. Suggesting that trial-demonstrated efficacy is sufficient to warrant large-scale deployment of pre-referral RAS ignores the paramount importance of functioning health systems for its delivery, for completing post-referral treatment, and for achieving complete cure. Presenting RAS as a "magic bullet" distracts from the most urgent priority: fixing health systems so they can provide a functioning continuum of care and save the lives of sick children.The data underlying our publication is freely accessible on Zenodo.

[A Randomized, Double-blind, Active-controlled Exploratory Clinical Trial for the Evaluation of the Efficacy and Safety of Goodmorning S Granule® on Constipation].

Background/Aims: Constipation is a common gastrointestinal disease that reduces the quality of life and incurs considerable medical expenses. Bisacodyl and sodium docusate are generally used to treat constipation. This study assessed the effectiveness and safety of Goodmorning S Granule® (Hanpoong Pharm. Co., Ltd., Wanju, Korea) in functional constipation by a comparison with bisacodyl. Methods: A 2-week randomized, double-blind, active-controlled exploratory clinical trial was conducted to compare the treatment (Goodmorning S Granule®) with the control (bisacodyl). The efficacy was measured by the changes in transition, Bristol stool type, stomachache, clinical manifestation, defecation time after drug consumption, 36-item short-form survey (SF-36), and the results of improvement evaluation. The safety was evaluated by the incidence of adverse drug events and vital signs. Additional analyses were conducted by dividing the severity according to the proportion of Bristol Stool Scale types 1 and 2. Results: Subjects were randomized to the treatment (n=24) or control (n=26) groups. No significant differences were observed in demographics. After 2 weeks from the baseline, the changes in the complete spontaneous bowel movement (CSBM) were higher in the treatment (4.00±2.62) group than in the control group (1.40±2.34) (p<0.05). The treatment group exhibited significant improvement in the score on the SF-36 questionnaire. The clinical side effects, such as stomachache and borborygmus, were reduced in the moderate constipation patients in the treatment group, according to additional analyses. Conclusions: Goodmorning S Granule®, a herbal medicine, was more effective in improving quality of life and CSBM per week and safer in the moderate constipation groups because of the reduced clinical side effects.

Bisacodyl Limits Chikungunya Virus Replication In Vitro and Is Broadly Antiviral.

Identifying novel antivirals requires significant time and resource investment, and the continuous threat of viruses to human health necessitates commitment to antiviral identification and development. Developing antivirals requires years of research and validation, and recent outbreaks have highlighted the need for preparedness in counteracting pandemics. One way to facilitate development is to repurpose molecules already used clinically. By screening such compounds, we can accelerate antiviral development. Here, we screened compounds from the National Institutes of Health's Developmental Therapeutic Program for activity against chikungunya virus, an alphavirus that is responsible for a significant outbreak in the Americas in 2013. Using this library, we identified several compounds with known antiviral activity, as well as several novel antivirals. Given its favorable in vitro activity and well-described in vivo activity, as well as its broad availability, we focused on bisacodyl, a laxative used for the treatment of constipation, for follow-up studies. We find that bisacodyl inhibits chikungunya virus infection in a variety of cell types, over a range of concentrations, and over several rounds of replication. We find that bisacodyl does not disrupt chikungunya virus particles or interfere with their ability to attach to cells, but, instead, bisacodyl inhibits virus replication. Finally, we find that bisacodyl is broadly antiviral against a variety of RNA viruses, including enteroviruses, flaviviruses, bunyaviruses, and alphaviruses; however, it exhibited no activity against the DNA virus vaccinia virus. Together, these data highlight the power of compound screening to identify novel antivirals and suggest that bisacodyl may hold promise as a broad-spectrum antiviral.

Bisacodyl: A review of pharmacology and clinical evidence to guide use in clinical practice in patients with constipation.

BACKGROUND: Bisacodyl is a member of the diphenylmethane family and is considered to be a stimulant laxative. It has a dual prokinetic and secretory action and needs to be converted into the active metabolite bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM) in the gut to achieve the desired laxative effect. Bisacodyl acts locally in the large bowel by directly enhancing the motility, reducing transit time, and increasing the water content of the stool. A recent network meta-analysis concluded that bisacodyl showed similar efficacy to prucalopride, lubiprostone, linaclotide, tegaserod, velusetrag, elobixibat, and sodium picosulfate for the primary endpoint of ≥3 complete spontaneous bowel movements (CSBM)/week and an increase of ≥1 CSBM/week over baseline. The meta-analysis also found that bisacodyl may be superior to the other laxatives for the secondary endpoint of change from baseline in the number of spontaneous bowel movements per week in patients with chronic constipation. This observation stimulated the authors to review the available literature on bisacodyl, which has been available on the market since the 1950 s. PURPOSE: The aim of the current review was to provide an overview of the historic background, structure, function, and mechanism of action of bisacodyl. Additionally, we discuss the important features and studies for bisacodyl to understand its peculiar characteristics and guide its use in clinical practice, but also stimulate research on open questions.

Chronic Constipation in the United States: Results From a Population-Based Survey Assessing Healthcare Seeking and Use of Pharmacotherapy.

OBJECTIVES: Chronic idiopathic constipation (CIC) is characterized by unsatisfactory defecation and difficult or infrequent stools. CIC affects 9%-20% of adults in the United States, and although prevalent, gaps in knowledge remain regarding CIC healthcare seeking and medication use in the community. We recruited a population-based sample to determine the prevalence and predictors of (i) individuals having discussed their constipation symptoms with a healthcare provider and (ii) the use of constipation therapies. METHODS: We recruited a representative sample of Americans aged 18 years or older who had experienced constipation. Those who met the Rome IV criteria for irritable bowel syndrome and opioid-induced constipation were excluded. The survey included questions on constipation severity, healthcare seeking, and the use of constipation medications. We used multivariable regression methods to adjust for confounders. RESULTS: Overall, 4,702 participants had experienced constipation (24.0% met the Rome IV CIC criteria). Among all respondents with previous constipation, 37.6% discussed their symptoms with a clinician (primary care provider 87.6%, gastroenterologist 26.0%, and urgent care/emergency room physician 7.7%). Age, sex, race/ethnicity, marital status, employment status, having a source of usual care, insurance status, comorbidities, locus of control, and constipation severity were associated with seeking care (P < 0.05). Overall, 47.8% of respondents were taking medication to manage their constipation: over-the-counter medication(s) only, 93.5%; prescription medication(s) only, 1.3%; and both over-the-counter medication(s) and prescription medication(s), 5.2%. DISCUSSION: We found that 3 of 5 Americans with constipation have never discussed their symptoms with a healthcare provider. Furthermore, the use of prescription medications for managing constipation symptoms is low because individuals mainly rely on over-the-counter therapies.

Characterization of the colonic response to bisacodyl in children with treatment-refractory constipation.

BACKGROUND: Colonic manometry with intraluminal bisacodyl infusion can be used to assess colonic neuromuscular function in children with treatment-refractory constipation. If bisacodyl does not induce high-amplitude propagating contractions (HAPCs), this can be an indication for surgical intervention. A detailed characterization of the colonic response to intraluminal bisacodyl in children with constipation may help to inform clinical interpretation of colonic manometry studies. METHODS: Studies were performed in five pediatric hospitals. Analysis included identification of HAPCs, reporting HAPCs characteristics, and an area under the curve (AUC) analysis. Comparisons were performed between hospitals, catheter type, placement techniques, and site of bisacodyl infusion. RESULTS: One hundred and sixty-five children were included (median age 10, range 1-17 years; n = 96 girls). One thousand eight hundred and ninety-three HAPCs were identified in 154 children (12.3 ± 8.8 HAPCs per child, 0.32 ± 0.21 HAPCs per min; amplitude 113.6 ± 31.5 mm Hg; velocity 8.6 ± 3.8 mm/s, propagation length 368 ± 175 mm). The mean time to first HAPC following bisacodyl was 553 ± 669 s. Prior to the first HAPC, there was no change in AUC when comparing pre- vs post-bisacodyl (Z = -0.53, P = .60). The majority of HAPCs terminated in a synchronous pressurization in the rectosigmoid. Defecation was associated with HAPCs (χ2 (1)=7.04, P < .01). Site of bisacodyl administration, catheter type, and hospital location did not alter the response. CONCLUSIONS AND INFERENCES: Intraluminal bisacodyl induced HAPCs in 93% of children with treatment-refractory constipation. The bisacodyl response is characterized by ≥1 HAPC within 12 minutes of infusion. The majority of HAPCs terminate in a synchronous pressurization in the rectosigmoid. Optimal clinical management based upon colonic manometry findings is yet to be determined.

Systematic scoping review of enhanced recovery protocol recommendations targeting return of gastrointestinal function after colorectal surgery.

BACKGROUND: Post-operative ileus (POI) and delayed return of gastrointestinal (GI) function are common complications after colorectal surgery. There is a lack of uniformity in enhanced recovery protocols (ERPs) with regards to interventions used to target these complications. This systematic review aims to categorize and summarize management recommendations available from published ERPs. METHODS: A systematic search of Ovid MEDLINE, Embase, Cochrane Library and PubMed databases was performed from January 1990 to May 2018. All studies publishing enhanced recovery or fast-track or multimodal pathway protocols for colorectal surgery in their full-text were included. Data on interventions aimed at reducing the duration of POI were extracted, as well as references quoted to support specific interventions. RESULTS: Of 481 manuscripts screened, 37 published ERPs were identified from 37 studies (18 cohort, seven historical-control, five guidelines, four randomized controlled trials, one randomized controlled trial protocol, one case series and one narrative review). The most commonly recommended interventions were magnesium-based laxatives (18 of 37, 48.6%), chewing gum (13 of 37, 35.1%), Alvimopan (6 of 37, 16.2%), lactulose (4 of 37, 10.8%), neostigmine (2 of 37, 5.4%) and bisacodyl (2 of 37, 5.4%). Geographical trends were noted for the various interventions, but high-quality evidence was only referenced to support the use of Alvimopan. CONCLUSION: ERP recommendations specific to interventions targeting POI and return of GI function are varied. While laxatives are the most commonly recommended intervention, there is only weak evidence reported to support this practice.

Long term treatment with stimulant laxatives - clinical evidence for effectiveness and safety?

OBJECTIVES: Bisacodyl and sodium picosulfate are classified both as stimulant laxatives, approved for short-term treatment of constipation and sold without prescription (OTC). Stimulant laxatives are associated with harmful long-term colonic effects and possible carcinogenic risk - and evidence support that these agents are used for longer periods. We aimed to compile and review the clinical trial evidence describing the effectiveness and safety of long-term treatment (>14 continuous days) with stimulant laxatives. METHODS: The PubMed database was searched for all randomised clinical trials (RCTs) examining the effect of bisacodyl or sodium picosulfate in adult patients diagnosed with constipation. RESULTS: Five RCTs (one open-label and four double-blinded) with intervention periods of four weeks duration were eligible. These included 1008 patients, whereof 26% dropped out. A positive global assessment of efficacy was obtained in 78-99% of the patients treated with bisacodyl or sodium picosulfate. Notably, the same global assessment was obtained in 46-54% of the placebo-treated patients. Compared to placebo, an improvement in stool consistency and a significant increase in number of bowel movements peer week were seen in favor of bisacodyl and sodium picosulfate. However, for pyridostigmine, a significant difference was seen compared to bisacodyl. AEs were generally mild, but frequent (up to 72%) mostly diarrhea and abdominal pain. CONCLUSION: The evidence base does not support use of stimulant laxatives for more than four weeks. Due to the substantial use of stimulant laxatives including sold OTC, longer term RCTs and epidemiological studies investigating effects and safety on the longer term are warranted.

Effect of bisacodyl on rats with slow transit constipation.

The effect of bisacodyl on the treatment of rats with slow transit constipation (STC) was studied. Forty-five female Wister rats were divided into control group, STC group, and STC bisacodyl group. The immunohistochemical method was used to determine interstitial cells of Cajal (ICC) and the expression of c-Kit protein. Body mass and the number of defecations were significantly decreased in the STC group compared with the control group on the 100th day after diphenoxylate administration, while dry weight of feces was significantly increased and the intestinal transit time was prolonged. There were significant differences in the number of defecations, dry weight of feces, and intestinal transit time among the three groups. The number of defecations was higher, dry weight of feces was lower, and intestinal transit time was shorter in the STC bisacodyl group compared to the STC group. In addition, ICC basement membrane dissolution occurred in the colon wall of the STC group. The connection between ICC and surrounding cells was destroyed, and the nucleus shrunken to different degrees. Moreover, c-Kit expression in the STC group was significantly lower than the control group. The connection between ICC and surrounding cells in the STC bisacodyl group was significantly stronger than the STC group, and the number of ICC and the expression of c-Kit were increased. Bisacodyl could reduce the severity of STC in rats by increasing the number of ICC and the expression of c-Kit.

Effect of bisacodyl on rats with slow transit constipation

The effect of bisacodyl on the treatment of rats with slow transit constipation (STC) was studied. Forty-five female Wister rats were divided into control group, STC group, and STC bisacodyl group. The immunohistochemical method was used to determine interstitial cells of Cajal (ICC) and the expression of c-Kit protein. Body mass and the number of defecations were significantly decreased in the STC group compared with the control group on the 100th day after diphenoxylate administration, while dry weight of feces was significantly increased and the intestinal transit time was prolonged. There were significant differences in the number of defecations, dry weight of feces, and intestinal transit time among the three groups. The number of defecations was higher, dry weight of feces was lower, and intestinal transit time was shorter in the STC bisacodyl group compared to the STC group. In addition, ICC basement membrane dissolution occurred in the colon wall of the STC group. The connection between ICC and surrounding cells was destroyed, and the nucleus shrunken to different degrees. Moreover, c-Kit expression in the STC group was significantly lower than the control group. The connection between ICC and surrounding cells in the STC bisacodyl group was significantly stronger than the STC group, and the number of ICC and the expression of c-Kit were increased. Bisacodyl could reduce the severity of STC in rats by increasing the number of ICC and the expression of c-Kit.

Colon-targeted delivery of solubilized bisacodyl by doubly enteric-coated multiple-unit tablet.

A doubly enteric-coated multiple-unit tablet (DET) of bisacodyl (BD) was formulated to selectively deliver the stimulant laxative to the large intestine. Solubilized BD in surfactants was adsorbed into the porous carrier and primarily coated with different combinations of pH-sensitive polymers (Eudragit S and Eudragit L) and time-dependent release polymer (Eudragit RS). BD-loaded granules were compressed into tablets and coated again with pH-sensitive polymers (Eudragit S:Eudragit L=1:1). The multiple-unit tablet was optimized with respect to the granular coating compositions (Eudragit S:Eudragit L:Eudragit RS=5:1:4) and coating level (12.5%), and coating level on the tablet (25%), by evaluating in vitro release profile in continuous dissolution medium. Drug release from the optimized tablet was effectively retarded in the simulated gastric and small intestinal fluids (below 7%), but profound drug liberation was attained in the colonic fluid (over 50%). On the other hand, drug release from the marketed product (Dulcolax®, Boehringer Ingelheim Pharma), a reference drug, in the gastric and small intestinal fluids was reached to 30%, while that in the colonic fluid was only 7%. In an in vivo efficacy study in loperamide-induced constipated rabbits, a remarkable recovery in fecal secretion was observed in the DET-treated group 24h post-dosing, compared to vehicle-treated (p<0.05) and the marketed product-treated groups (p<0.05). Moreover, pharmacokinetic evaluation in the constipated rabbits revealed that the DET system significantly lowered the systemic exposure compared with the marketed product (p<0.05), by hindering drug release in the upper intestine, a preferential absorption site. Therefore, the novel colon-targeted delivery system may be an alternative for boosting pharmacological responses in the colon, while diminishing the intestinal irritation and/or systemic adverse effect of the stimulant laxative.

[Bisacodyl as laxative in Belgian pharmacy]. / Le laxalif bisacodyl dans les pharmacies belges.

Obstipation is a common complaint in pharmacies and one of the treatment strategies is the delivery of enteric coated bisacodyL tablets. This article reviews the different aspects that are important for pharmacists to guarantee patient safety: whether medical treatment is required or not, which advice should be given on how to use the drug, and to conclude what is the analytical quality of the commercial products on the Belgian market.

Prospective, randomized comparison of same-day dose of 2 different bowel cleanser for afternoon colonoscopy: picosulfate, magnesium oxide, and citric acid versus polyethylene glycol.

For afternoon colonoscopy, same-day administration of sodium picosulfate, magnesium oxide, and citric acid (PM/Ca) is recommended. However, few studies have evaluated the bowel-cleansing efficacy and safety of this regimen. The aim of this study was to compare the bowel-cleansing efficacy, side effects, and patient's tolerability of a same-day split administration of PM/Ca with polyethylene glycol (PEG) for afternoon colonoscopy. Patients were randomly assigned to a PM/Ca group or a PEG group. The PM/Ca group consumed 1 sachet of PM/Ca at 06:00 and 1 sachet of PM/Ca 4 hours before the colonoscopy. They also took 2 tablets of bisacodyl before sleep on the night before. The PEG group consumed 2 L of PEG at 06:00 and 2 L of PEG 4 hours before the colonoscopy. All subjects were instructed to finish the bowel cleanser or fluid at least 2 hours before colonoscopy. All colonoscopic examinations were performed in the afternoon on the same day. The bowel-cleansing efficacy was scored using 2 scales: the Ottawa Bowel Preparation Scale (OBPS) and the Aronchick scale. Ease of using the bowel cleanser was rated from 1 (very easy) to 5 (very difficult). Two hundred nine patients underwent colonoscopy. The bowel-cleansing scores by OBPS did not differ between groups (5.0 vs 4.9, P = 0.63). Ease of using the bowel cleanser was superior in the PM/Ca group (P < 0.01). The cleansing efficacy of PM/Ca administered on the day of colonoscopy is comparable to that of PEG. Patients prefer PM/Ca.

The use of low-volume polyethylene glycol containing ascorbic acid versus 2 L of polyethylene glycol plus bisacodyl as bowel preparation for colonoscopy.

OBJECTIVE: Low-volume polyethylene glycol (PEG) bowel preparations have been developed to improve compliance for colonoscopy. Our study aimed to compare the efficacy and tolerability of low-volume PEG containing ascorbic acid for colonoscopy against 2 L of PEG plus bisacodyl. METHODS: We prospectively enrolled consecutive inpatients who had not undergone polypectomy at the index colonoscopy and were subsequently referred for polypectomy at our hospital. A total of 62 patients were randomized to receive either low-volume PEG containing ascorbic acid (n = 31) or 2 L of PEG plus bisacodyl (n = 31) as a split-dose regimen in inpatients. The efficacy of preparation was determined using the Ottawa Bowel Preparation Score (OBPS) and a 4-point scale. Adverse events, tolerability, and willingness were evaluated using a questionnaire. RESULTS: Based on the OBPS and 4-point scale, we determined that the efficacy of low-volume PEG containing ascorbic acid was comparable to that of the 2 L of PEG plus bisacodyl (p = 0.071 for OBPS, p = 0.056 for the 4-point scale). Adverse events were comparable between the two groups (p = 1.000). A greater proportion of patients in the low-volume PEG containing ascorbic acid (90.6%) and the 2L of PEG plus bisacodyl (96.9%) were willing to repeat the same preparation for subsequent colonoscopy. CONCLUSION: Low-volume PEG containing ascorbic acid had comparable efficacy and tolerability to 2 L of PEG plus bisacodyl, when given as a split dose, for colonoscopy in inpatients. Split-dose low-volume PEG containing ascorbic acid is a good alternative for bowel preparation for colonoscopy in inpatients.

[Efficacy of bisacodyl given as part of a polyethylene glycol-based bowel preparation prior to colonoscopy in hospitalized patients: a prospective ramdomized trial].

BACKGROUND/AIMS: Inpatient status can cause inadequate bowel preparation. The majority of previous studies regarding bowel preparation have focused on comparing the effects of different purgative regimens in outpatients. However, data on bowel preparation for inpatients are lacking. The aim of this study was to investigate whether bisacodyl plus polyethylene glycol (PEG) can improve bowel preparation in hospitalized patients. METHODS: A prospective, randomized and observer-blind study was performed. A total of 196 hospitalized patients undergoing colonoscopy were randomized to receive 4 L PEG (PEG only group) or 4 L PEG＋bisacodyl 10 mg (bisacodyl added group). The adequacy of bowel preparation was scored using the Ottawa bowel preparation scale. RESULTS: One hundred and eighty-three subjects completed the study; 96 in the bisacodyl added group and 87 in the PEG only group. There were no significant differences between the bisacodyl added group and the PEG only group with respect to the score of bowel cleansing (3.59±B1;2.81 vs. 3.82±B1;3.03, p=0.607), quality of bowel cleansing (adequate preparation 89.6% vs. 85.1%, p=0.380), and overall adverse events (66.7% vs. 52.9%, p=0.057). However, a larger proportion of patients in the PEG only group were able to ingest the entire solution as prescribed than in the bisacodyl added group (98.9% vs. 75.0%, p<0.001). CONCLUSIONS: In hospitalized patients, the quality of bowel preparation did not differ depending on whether bisacodyl is added or not. In addition, patient compliance based on consumption of cleansing agent was better in the PEG only group.

Systematic review of stimulant and nonstimulant laxatives for the treatment of functional constipation.

BACKGROUND: Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided treatments and prevention strategies to patients for chronic constipation despite the significant variation in both medical and personal perceptions of the condition. OBJECTIVE: To review relevant research evidence from clinical studies investigating the efficacy and safety of commercially available pharmacological laxatives in Canada, with emphasis on studies adopting the Rome criteria for defining functional constipation. SEARCH METHODS: PubMed, Medline, Embase and Evidence-Based Medicine Reviews databases were searched for blinded or randomized clinical trials and meta-analyses assessing the efficacy of nonstimulant and stimulant laxatives for the treatment of functional constipation. RESULTS: A total of 19 clinical studies and four meta-analyses were retrieved and abstracted regarding study design, participants, interventions and outcomes. The majority of studies focused on polyethylene glycol compared with placebo. Both nonstimulant and stimulant laxatives provided better relief of constipation symptoms than placebo according to both objective and subjective measures. Only one study compared the efficacy of a nonstimulant versus a stimulant laxative, while only two reported changes in quality of life. All studies reported minor side effects due to laxative use, regardless of treatment duration, which ranged from one week to one year. Laxatives were well tolerated by both adults and children.

A randomized, controlled trial of oral sulfate solution plus polyethylene glycol as a bowel preparation for colonoscopy.

BACKGROUND: No bowel preparation for colonoscopy is optimal with regard to efficacy, safety, and tolerability. New options for bowel preparation are needed. OBJECTIVE: To compare a new hybrid preparation consisting of a reduced dose of oral sulfate solution (OSS) plus 2 L of sulfate-free electrolyte lavage solution (SF-ELS) with 2 low-volume preparations based on polyethylene glycol electrolyte lavage solution (PEG-ELS). DESIGN: Two randomized, controlled trials. SETTING: Twenty-four U.S. centers. PATIENTS: A total of 737 outpatients undergoing colonoscopy. INTERVENTIONS: In study 1, OSS plus SF-ELS was given as a split dose, and in study 2, OSS plus SF-ELS was given in its entirety the evening before colonoscopy. In study 1, the active control was 2 L of PEG-ELS plus ascorbic acid (PEG-EA) given as a split dose. In study 2, the control was 10 mg of bisacodyl plus 2 L of SF-ELS taken the evening before colonoscopy. MAIN OUTCOME MEASUREMENTS: Rates of successful (good or excellent) bowel preparation. RESULTS: In study 1, the rates of successful (excellent or good) preparation with OSS plus SF-ELS and PEG-EA were identical at 93.5% for split-dose preparation. OSS plus SF-ELS was noninferior to PEG-EA (P < .001). In study 2, OSS plus SF-ELS resulted in successful preparation in 89.8% of patients compared with 83.5% with bisacodyl plus SF-ELS in a same-day preparation regimen. OSS plus SF-ELS was noninferior to bisacodyl plus SF-ELS (P <.001). In study 1, vomiting was more frequent with OSS plus SF-ELS (13.5% vs 6.7%; P = .042), and bloating was rated worse with PEG-EA (P = .025). In study 2, overall discomfort was rated worse with OSS plus SF-ELS (mean score 2.1 vs 1.8; P = .032). There were no deaths in either study and no serious adverse events considered related to the preparation. LIMITATIONS: Bowel cleansing was not scored by colon segment. Adenoma detection was not compared between the regimens. CONCLUSION: OSS plus SF-ELS is a new, safe, and effective bowel preparation for colonoscopy.

Pilot study on efficacy of reduced cathartic bowel preparation with polyethylene glycol and bisacodyl.

AIM: To evaluate the efficacy of reduced cathartic bowel preparation with 2 L polyethylene glycol (PEG)-4000 electrolyte solution and 10 mg bisacodyl enteric-coated tablets for computed tomographic colonography (CTC). METHODS: Sixty subjects who gave informed consent were randomly assigned to study group A, study group B or the control group. On the day prior to CTC, subjects in study group A were given 20 mL 40% wt/vol barium sulfate suspension before 3 mealtimes, 60 mL 60% diatrizoate meglumine diluted in 250 mL water after supper, and 10 mg bisacodyl enteric-coated tablets 1 h before oral administration of 2 L PEG-4000 electrolyte solution. Subjects in study group B were treated identically to those in study group A, with the exception of bisacodyl which was given 1 h after oral PEG-4000. Subjects in the control group were managed using the same strategy as the subjects in study group A, but without administration of bisacodyl. Residual stool and fluid scores, the attenuation value of residual fluid, and discomfort during bowel preparation in the three groups were analyzed statistically. RESULTS: The mean scores for residual stool and fluid in study group A were lower than those in study group B, but the differences were not statistically significant. Subjects in study group A showed greater stool and fluid cleansing ability than the subjects in study group B. The mean scores for residual stool and fluid in study groups A and B were lower than those in the control group, and were significantly different. There was no significant difference in the mean attenuation value of residual fluid between study group A, study group B and the control group. The total discomfort index during bowel preparation was 46, 45 and 45 in the three groups, respectively, with no significant difference. CONCLUSION: Administration of 10 mg bisacodyl enteric-coated tablets prior to or after oral administration of 2 L PEG-4000 electrolyte solution enhances stool and fluid cleansing ability, and has no impact on the attenuation value of residual fluid or the discomfort index. The former is an excellent alternative for CTC colorectum cleansing.