Effect of loperamide and naloxone on mouth-to-caecum transit time evaluated by lactulose hydrogen breath test.

Basilisco, Guido; Bozzani, A; Camboni, Gabriella; Recchia, Martino; Quatrini, M; Conte, Dario; Penagini, Roberto; Bianchi, P.

doi:10.1136/gut.26.7.700

Cited by 57 publications

(21 citation statements)

References 17 publications

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“…In each session, gastrointestinal transit time was assessed by measuring pulmonary hydrogen (Bond and Levitt, 1975;Basilisco et al, 1985Basilisco et al, , 1987. This method, which was successfully used in our previous methylnaltrexone studies (Yuan et al, 1996(Yuan et al, , 2000, is based on the measurement of hydrogen produced in exhaled air when unabsorbable disaccharide (lactulose) is fermented by colonic bacteria.…”

Section: Methodsmentioning

confidence: 99%

Effects of Subcutaneous Methylnaltrexone on Morphine-Induced Peripherally Mediated Side Effects: A Double-Blind Randomized Placebo-Controlled Trial

Yuan¹,

Wei²,

Foss³

et al. 2002

J Pharmacol Exp Ther

111

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Methylnaltrexone, the first peripheral opioid receptor antagonist, has the potential to prevent or reverse opioid-induced peripherally mediated side effects without affecting analgesia. In previous human trials, we demonstrated that intravenous methylnaltrexone prevented morphine-induced delay in gastrointestinal transit time. We also observed that the compound decreased some of the morphine-induced troublesome subjective effects. However, the effects of subcutaneous methylnaltrexone, a more convenient route of administration, have not been evaluated. In this controlled trial, we evaluated the efficacy of subcutanous methylnaltrexone in antagonizing morphine-induced delay in oral-cecal transit time. In addition, opioid-induced unpleasant subjective effects and pharmacokinetics were studied. We observed that in the first group (n ϭ 6) morphine (0.05 mg/kg intravenously) increased the transit time from a baseline level of 85 Ϯ 20.5 min to 155 Ϯ 27.9 min (mean Ϯ S.D., P Ͻ 0.01). After 0.1 mg/kg subcutaneous methylnaltrexone plus morphine, the transit time reduced to 110 Ϯ 41.0 min. In the second group (n ϭ 6), morphine increased the transit time from a baseline level of 98 Ϯ 49.1 min to 140 Ϯ 58.2 min (P Ͻ 0.01). After 0.3 mg/kg subcutaneous methylnaltrexone plus morphine, the transit time reduced to 108 Ϯ 59.6 min (P Ͻ 0.05 compared with placebo plus morphine). In addition, subcutaneous methylnaltrexone significantly decreased morphineinduced subjective rating changes. Pharmacokinetic data after subcutaneous drug injection were compared to the data obtained from previous intravenous and oral administrations. Our results suggest that subcutaneous methylnaltrexone may have clinical utility in treating opioid-induced constipation and reducing opioid-induced unpleasant subjective symptoms.

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Section: Methodsmentioning

confidence: 99%

Effects of Subcutaneous Methylnaltrexone on Morphine-Induced Peripherally Mediated Side Effects: A Double-Blind Randomized Placebo-Controlled Trial

Yuan¹,

Wei²,

Foss³

et al. 2002

J Pharmacol Exp Ther

111

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“…ducing constipation [43]. As compared to placebo, loperamide prolonged significantly the orocaecal transit time (breath hydrogen test after ingestion of lactulose) [44] [45].…”

Section: Risk Of Bias Across Studiesmentioning

confidence: 99%

Racecadotril Efficacy in the Symptomatic Treatment of Adult Acute Diarrhoea: A Systematic Review and Meta-Analysis

Vetel¹,

Hamza²,

Coffin³

et al. 2014

IJCM

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The efficacy of racecadotril (RC), an intestinal antisecretory drug acting via an enkephalinase inhibition, was reviewed in paediatric acute diarrhoea but not yet in adults. Objective: To estimate the effectiveness of RC in the symptomatic treatment of acute diarrhoea in adults. Data Sources: A systematic review of MedLine, Cochrane Controlled Trials Register, DARE, and Embase (up to November 2013). Additional studies were identified by contacting clinical experts and the manufacturer. Study Selection and Appraisal: Randomized Controlled Trials performed in adults suffering from acute diarrhoea using RC in one treatment arm. Independent extraction of articles using predefined data fields, and methodological quality measurement assessment. All randomised trials performed in adults suffering from acute diarrhoea with RC as the studied group. Statistics: The main efficacy endpoint was diarrhoea duration defined as time to recovery compared between groups by survival techniques and converted into hazard ratio (HR). We exclusively used a random-effect meta-analytic model. Constipation proportion was the main safety endpoint, evaluated between treatments by the Relative Risks (RR). Results: Twelve randomised trials (2619 patients) met inclusion criteria. Duration of diarrhoea was much shorter in the RC group, the proportion of patients having recovered at any time of the treatment period was 65% higher in the RC group, compared with placebo (HR = 1 362to placebo, RC is characterized by a clinically relevant earlier remission of diarrhoea. When compared to loperamide, diarrhoea duration was similar, however, significantly fewer secondary constipation adverse effects were observed.

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“…In humans, loperamide has been found to stimulate jejunal motility by increasing the frequency of the phase 3 migrating motor com-plexes23 and to delay orocaecal transit time. 4 Its action on intestinal fluid absorption, however, is not clearly established. In vitro or in anaesthetised animals, loperamide has been found to inhibit intestinal secretion induced by thermostable Escherichia coli,' cholera toxin,6 deoxycholic acid,7 and prostaglandin89 but not by vasoactive intestinal polypeptide or mannitol.…”

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confidence: 99%

Absorptive and motor components of the antidiarrhoeal action of loperamide: an in vivo study in pigs.

Theodorou¹,

Fioramonti²,

Hachet³

et al. 1991

Gut

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The effects of loperamide (0.1 mg/kg orally) on net colonic water absorption, orocolonic transit time, and intestinal motility were investigated in pigs chronically fitted either with two cannulas in the proximal colon and a catheter in the duodenum and the ileum or with intraparietal electrodes on the duodenum, jejunum, caecum, and proximal colon and a duodenal catheter. Loperamide, given 20 minutes before a meal reduced significantly colonic net water absorption for 10 hours after eating. It also reduced colonic flow rate, increased orocolonic transit time, modified the postprandial intestinal motility by inducing supplementary phase 3 motor complexes and did not affect caecocolonic motility. Intraduodenal infusion of a hypertonic solution of mannitol (900 mOsmfl; 0.6 mi/minute) for the first postprandial hour strongly reduced or reversed net colonic water absorption, increased the colonic flow rate, accelerated the orocolonic transit, and induced profuse diarrhoea. After loperamide administration, all these effects were blocked and the relative colonic water absorption, expressed as the fraction of flow entering the colon, was strongly increased. Mannitol did not modify motility of the small and large intestine, and supplementary phase 3 motor complexes were observed when mannitol infusion was preceded by loperamide administration. It is concluded that in experimental osmotic diarrhoea loperamide causes a reduction in digesta flow entering into the colon, mediated by its action on small intestinal motility, and an increase in colonic water absorption.

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Effect of loperamide and naloxone on mouth-to-caecum transit time evaluated by lactulose hydrogen breath test.

Cited by 57 publications

References 17 publications

Effects of Subcutaneous Methylnaltrexone on Morphine-Induced Peripherally Mediated Side Effects: A Double-Blind Randomized Placebo-Controlled Trial

Effects of Subcutaneous Methylnaltrexone on Morphine-Induced Peripherally Mediated Side Effects: A Double-Blind Randomized Placebo-Controlled Trial

Racecadotril Efficacy in the Symptomatic Treatment of Adult Acute Diarrhoea: A Systematic Review and Meta-Analysis

Absorptive and motor components of the antidiarrhoeal action of loperamide: an in vivo study in pigs.

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