Chris Schuijt

The burden of constipation on quality of life: results of a multinational survey

Background The impact of constipation on quality of life (QoL) may vary in different cultural or national settings.

A multinational survey of prevalence and patterns of laxative use among adults with self‐defined constipation

Background  While numerous studies report prevalence of constipation, use of laxatives is poorly understood.

Efficacy and safety of bisacodyl in the acute treatment of constipation: a double‐blind, randomized, placebo‐controlled study

Although laxatives are a first‐line treatment for constipation, there are few randomized placebo‐controlled trials assessing their efficacy.

Ibuprofen Extrudate, a Novel, Rapidly Dissolving Ibuprofen Formulation: Relative Bioavailability Compared to Ibuprofen Lysinate and Regular Ibuprofen, and Food Effect on All Formulations

N anti-inflammatory drugs (NSAIDs), including ibuprofen, have been used for decades in the management of a multitude of pain conditions and rheumatic diseases. Their effects include inhibition of prostaglandin synthesis resulting in analgesic, anti-inflammatory, and antipyretic efficacy. Because of a longstanding and favorable safety record as well as proven efficacy in many different populations and indications, the popularity of ibuprofen is ever increasing. The vast majority of indications for pain treatment requires an onset of action as quickly as possible. For an oral administration drug, the time to onset of a desired pharmacological effect depends on many successive steps: dissolution of the formulation, passage to the site of absorption (usually the jejunal parts of the small intestine), permeation through physiological membranes, entry into the portal vein circulation (with potential enteric or hepatic first-pass metabolism), distribution from plasma to the site of action, and interaction with the receptor, which then causes a cascade of events leading to the targeted pharmacological modification. Distribution to other tissues, metabolism, and excretion of the active principle may also affect early availability of the drug at the effector site. For many compounds, the initial rise of the plasma concentration, following oral administration, is critical with regard to time to onset of the desired pharmacological effect. Ibuprofen shows low solubility in aqueous acidic media but is highly permeable through physiological membranes. Bioavailability is close to 100% because of almost complete absorption, but the onset of absorption strongly depends on dissolution and thus on the administered formulation. Different approaches have been made to improve solubility of the active ingredient, such as transferring the substance to a salt (lysinate) or designing a pharmaceutical dosage form that favors a quick release of ibuprofen in the gastrointestinal tract. In the manufacture of ibuprofen extrudate tablets, a special extrusion technology is applied to provide the BRIEF REPORTS/PHARMACOKINETICS

Survey of laxative use by adults with self-defined constipation in South America and Asia: a comparison of six countries

Background  In contrast to the US and Europe, prevalence and laxative use for self‐defined constipation among adults was previously reported to be unassociated with age among adults in South Korea and Brazil.

Comparison of bisacodyl and sodium picosulphate in the treatment of chronic constipation

ABSTRACT Background: Chronic constipation is a widespread condition. Although laxatives are generally accepted as being effective treatments, few studies have made formal comparisons of their efficacy and safety in chronic use. Objective: To compare the safety and efficacy of bisacodyl and sodium picosulphate in the treatment of chronic constipation over a 4-week period. Methods: Patients with chronic constipation (N = 144), recruited from out-patient clinics, were analysed for safety and efficacy in this open-label, randomised, parallel-group study. Patients were treated daily for 4 weeks (bisacodyl, 5–10 mg daily: 70 patients; sodium picosulphate, 5–10 mg daily: 74 patients). Primary efficacy criteria consisted of the number of bowel movements and stool consistency. Secondary efficacy criteria were straining at stool and physicians’ global efficacy assessment. Safety assessments included adverse event monitoring, tolerability and changes in laboratory parameters. Results: Both treatments were equally effective in treating chronic constipation, providing sustained improvement in symptoms. Compared to baseline, there were significant ( p < 0.001) improvements in stool frequency and consistency and in the occurrence of straining at 14 and 28 days for both treatment groups. Based on the physicians’ global assessment, a significant improvement was observed in 74.6% (bisacodyl) and 79.2% (sodium picosulphate) of patients. Neither treatment had significant effects on serum electrolytes. There was a trend for better tolerability in patients receiving bisacodyl treatment based on the number of drug-related adverse events (bisacodyl: 7; sodium picosulphate: 14, two patients withdrawn). Conclusions: Bisacodyl and sodium picosulphate are equally well tolerated and effective in the treatment of chronic constipation over a 4-week period.

Sodium picosulfate in opioid-induced constipation: results of an open-label, prospective, dose-ranging study.

Identification of a safe and effective dose of the laxative sodium picosulfate was investigated in a single-centre, open-label study of 23 patients (age 40-81 years) receiving / 60 mg/day morphine sulphate and experiencing constipation. A starting dose of 5, 10 or 15 mg sodium picosulfate (1 mg/mL solution) was administered, based on the patient’s clinical status at entry and recent requirements for laxatives. Dose titration was permitted (9 / 2.5 or 5 mg increments), to a maximum daily dose of 60 mg. Bowel movements, concomitant medication and need for suppositories or enemas were recorded in daily diaries. Sixteen patients withdrew before the end of the planned 14-day treatment period because of deterioration of the underlying condition. Sodium picosulfate was well-tolerated. Serious adverse events were all related to the underlying condition. A satisfactory response (normal stool consistency, not requiring enemas, suppositories or manual evacuation, no significant adverse event) was achieved in 15/20 evaluable patients. The median daily dose to achieve this was 15 mg (range: 5-30 mg) and the median time to first bowel movement after dosing was 11.75 hours (range: 6-22.5 hours). There was no clear relationship between the opioid dose and the optimum dose of sodium picosulfate, confirming that individual dose titration is necessary.

Randomised, placebo-controlled, double-blind study to investigate the efficacy and safety of the acute use of sodium picosulphate in patients with chronic constipation.

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.

M1217 Diet and Physical Activity in Constipation Revisited - Too Little or Too Much?

capture important symptom change. To address this, we developed a daily diary version of the GCSI. The aim of this study was to compare the responses of this daily GCSI diary to the GCSI using the conventional 2 week recall period. Methods: 12 patients with confirmed delayed gastric emptying were recruited from one clinical center; 5 were diabetic, 75% women, 100% Caucasian with average age of 43.9 (SD=10.6) years (range 25 to 62 years). Patients recorded their symptoms using the daily GCSI diary over a 2 week period, and then filled the conventional GCSI using a 2 week recall period. The daily GCSI scores were compared with the 2-week recall GCSI scores. Variability over the 2 weeks was calculated as the standard deviation of the daily scores for each patient. Results: Daily variability was present in the individual symptoms, the subscores, and the daily GCSI scores. For the 12 patients, the average of the daily GCSI scores (1.4±0.9 [SD]) compared well to the 2 week recall GCSI (1.6±1.0; p>0.10). The daily variation over 2 weeks is indicated by the 0.9 SD of the individual diary patient scores. Interestingly, the 2 week recall GCSI correlated extremely well with the average daily GCSI scores over 2 weeks (r=0.931; p<0.001) and was better than the correlation of the 2 week recall GCSI with the daily diary GCSI score for the last day (r=0.785; p=0.002) when the 2 week recall GCSI was assessed. In comparing the 2 week recall versus the daily diary for the GCSI subscores, there was excellent correlation in the postprandial/early satiety subscore (r=0.956) and bloating subscore (0.945). The N/ V subscore had good correlation (r=0.890) with high correlation coefficients for the symptoms of nausea (r=0.961) and retching (r=0.961), but a lower coefficient for vomiting (r=0.633). Conclusions: The GCSI daily diary captures daily variability of gastroparetic symptoms. Even so, the conventional GCSI using a 2 week recall is well correlated with the average of the GCSI daily diary over 2 weeks. Thus, the conventional 2 week diary captures patients overall experience with their symptoms, but the daily diary can capture more rapidly occurring changes in symptoms. TheGCSI has the characteristics to be a good patient reported outcome for evaluating the effectiveness of treatments in clinical trials for gastroparesis.