Dataset Information

A critical appraisal of lubiprostone in the treatment of chronic constipation in the elderly.

ABSTRACT: Chronic constipation is a common disorder in the general population, with higher prevalence in the elderly, and is associated with worse quality of life and with greater health care utilization. Lubiprostone is an intestinal type-2 chloride channel activator that increases intestinal fluid secretion, small intestinal transit, and stool passage. Lubiprostone is currently approved by the US Food and Drug Administration for the treatment of chronic idiopathic constipation and of irritable bowel syndrome with predominant constipation. This review outlines current approaches and limitations in the treatment of chronic constipation in the elderly and discusses the results, limitations, and applicability of randomized, controlled trials of lubiprostone that have been conducted in the general and elderly population, with additional focus on the use of lubiprostone in constipation in Parkinson's disease and in opioid-induced constipation, two clinical entities that can be comorbid in elderly patients.

SUBMITTER: Gras-Miralles B

PROVIDER: S-EPMC3578442 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A critical appraisal of lubiprostone in the treatment of chronic constipation in the elderly.

Gras-Miralles Beatriz B Cremonini Filippo F

Clinical interventions in aging 20130215

Chronic constipation is a common disorder in the general population, with higher prevalence in the elderly, and is associated with worse quality of life and with greater health care utilization. Lubiprostone is an intestinal type-2 chloride channel activator that increases intestinal fluid secretion, small intestinal transit, and stool passage. Lubiprostone is currently approved by the US Food and Drug Administration for the treatment of chronic idiopathic constipation and of irritable bowel syn ...[more]

PMID: 23439964

Similar Datasets

Project description:ObjectivesThis multicenter, phase 3 trial evaluated oral lubiprostone for constipation associated with non-methadone opioids in patients with chronic noncancer-related pain.MethodsAdults with opioid-induced constipation (OIC; <3 spontaneous bowel movements [SBMs] per week) were randomized 1:1 to double-blind lubiprostone 24??g or placebo twice daily for 12 weeks. The primary end point was the overall SBM response rate. Responders had at least moderate response (?1 SBM improvement over baseline frequency) in all treatment weeks with available observed data, as well as full response (?3 SBMs per week) for at least 9 of the 12 treatment weeks.ResultsIn total, 431 patients were randomized; 212 each received lubiprostone and placebo, and 7 were not treated. Overall, the SBM response rate was significantly higher for patients treated with lubiprostone vs. placebo (27.1 vs. 18.9%, respectively; P=0.030). Overall mean change from baseline in SBM frequency was significantly greater with lubiprostone vs. placebo (3.2 vs. 2.4, respectively; P=0.001). The median time to first SBM was significantly shorter with lubiprostone vs. placebo (23.5 vs. 37.7?h, respectively; P=0.004). Compared with placebo, the patients treated with lubiprostone exhibited significant improvements in straining (P=0.004), stool consistency (P<0.001), and constipation severity (P=0.010). No significant differences were observed in quality-of-life measures or the use of rescue medication; however, the percentage of patients who used rescue medication was consistently lower in the lubiprostone group than in the placebo group at months 1 (34.9 vs. 37.7%), 2 (23.4 vs. 26.6%), and 3 (20.5 vs. 22.0%). Adverse events (AEs) >5% were diarrhea, nausea, vomiting, and abdominal pain (lubiprostone: 11.3, 9.9, 4.2, and 7.1%, respectively; placebo, 3.8, 4.7, 5.2, and 0%, respectively). None of the serious AEs (lubiprostone, 3.3%; placebo, 2.8%) were related to lubiprostone.ConclusionsLubiprostone significantly improved symptoms of OIC and was well tolerated in patients with chronic noncancer pain.

Project description:Background Tobacco use is a leading preventable cause of morbidity and mortality globally. Clinical practice guidelines for the treatment of tobacco use dependence are of varied scope and quality, making it challenging for users to select and apply recommendations. Objective The study objective is to identify and critically appraise the quality of existing clinical practice guidelines for tobacco cessation. Setting The study occurred between collaborative academic institutions located in Qatar and New Zealand. Methods A systematic literature search was performed for the period 2006-2018 through the following databases: PubMed, EMBASE, CINAHL, ISI Web of Science, Scopus, National Guideline Clearing House, Campbell Library, Health System Evidence, Joanna Briggs Institute Evidence-Based Practice Database, Academic Search Complete, ProQuest, PROSPERO, and Google Scholar. Relevant professional societies' and health agencies' websites were also searched. Two reviewers independently extracted and assessed guidelines' quality using Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument. Main outcome measure Standardized domain scores according to the AGREE II instrument. Results 7741 hits were identified. After removing duplicates and screening, 24 guidelines were included. Highest guideline quality was for National Institute for Health and Care Excellence (NICE) guideline with an overall ranking score of 87.56% and least quality was for Japanese Circulation Society Joint Working Group with an overall score of 29.34%. Domain 4 of AGREE II (clarity of presentation) had the highest average quality score (70.95%), while the lowest average quality scores were for Domain 2 (Rigour of Development) (50.21%) and Domain 5 (Applicability) (45.05%). Conclusion Seven guidelines were judged to be of high quality (overall score of ≥ 70%). Future guidelines for tobacco dependence treatment should use rigorous methods of development and provide applicable recommendations.

Project description:IntroductionLubiprostone capsules are approved for managing three different chronic constipation conditions. A "sprinkle" formulation may facilitate use in individuals with difficulty swallowing capsules. Our objective was to evaluate the bioequivalence, pharmacokinetics (PK), and bioavailability of lubiprostone sprinkles vs lubiprostone capsules, compared with placebo.MethodsA 1-week randomized, placebo-controlled, double-blinded, bioequivalence study (study 302) and a single-dose PK and bioavailability crossover study (study 304) were conducted. In study 302, 522 subjects with chronic constipation were randomized to lubiprostone sprinkle 24 μg twice daily (BID), lubiprostone capsule 24 μg BID, or placebo. The primary efficacy endpoint was observed spontaneous bowel movement (SBM) counts (equivalence defined as showing the 90% confidence interval [CI] of the "between-group SBM ratio" to be contained within 0.8-1.25). Study 304 included two cohorts of healthy volunteers randomized to a single 48-μg lubiprostone dose, sprinkle, or capsule (n = 35) or to a single 48-μg sprinkle dose, in fed or fasted state (n = 14).ResultsBoth lubiprostone formulations significantly improved SBM count (sprinkle, 4.82 ± 3.66, P = 0.002; capsule, 5.74 ± 3.79, P < 0.0001) vs placebo (3.68 ± 2.16), but equivalent efficacy was not demonstrated, with a 90% CI for the SBM count ratio of 0.69-0.95. Quantifiable PK data on lubiprostone were limited; however, overall exposure to the M3 metabolite was approximately 44% higher with sprinkles vs capsules under fasted conditions (geometric mean ratio 1.441 [90% CI, 1.166, 1.782]), and exposure with the sprinkle formulation was 11% lower in the fed state vs the fasted state (geometric mean ratio 0.888 [90% CI, 0.675, 1.168]). Both formulations were generally well tolerated.ConclusionDespite the significant improvement in SBM counts vs placebo, the sprinkle formulation did not demonstrate bioequivalence to the capsule formulation in either pharmacodynamic or PK key parameters.Trial registrationStudy 302: ClinicalTrials.gov identifier, NCT03097861; https://www.clinicaltrials.gov/ct2/show/NCT03097861 ; Study 304: ClinicalTrials.gov identifier, NCT03010631; https://www.clinicaltrials.gov/ct2/show/NCT03010631 .

Dataset Information

A critical appraisal of lubiprostone in the treatment of chronic constipation in the elderly.

Publications

A critical appraisal of lubiprostone in the treatment of chronic constipation in the elderly.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets