Racecadotril

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Jeannemarie Lecomte - One of the best experts on this subject based on the ideXlab platform.

  • effects of Racecadotril and loperamide on bacterial proliferation and on the central nervous system of the newborn gnotobiotic piglet
    Alimentary Pharmacology & Therapeutics, 2001
    Co-Authors: Yvonne Duvaliflah, P Baumer, H Berard, P Guillaume, P Raibaud, Y Joulin, Jeannemarie Lecomte
    Abstract:

    Methods The effects of 4 days of oral administration of different doses of two drugs, an enkephalinase inhibitor (the antisecretory agent, Racecadotril) and a μ-receptor agonist (loperamide), on intestinal growth of a bacterial nonpathogenic strain (Escherichia coli E 404) and on the central nervous system (CNS) were compared in newborn gnotobiotic piglets. Results The E. coli content of the proximal jejunum (segment S1) and the E. coli ratio of stomach:segment S1 were similar in the Racecadotril (20 mg/kg b.d., n = 5) and control groups. In contrast, in the loperamide group (1 mg/kg b.d., n = 4), the E. coli content of segment S1 and the E. coli ratio stomach:S1 were both significantly higher than with Racecadotril or control (P = 0.04 and 0.005, respectively, for E. coli content; P = 0.05 and 0.03, respectively, for stomach:S1). There were no clinical signs of neurotoxicity and no deaths with Racecadotril given orally at a high dose of 130 mg/kg b.d. (n = 5) – nearly 60 times the paediatric dosage. In contrast, an equivalent high dose of loperamide (5 mg/kg b.d.) resulted in death in three out of four piglets. Conclusions In contrast to loperamide, Racecadotril did not induce bacterial overgrowth and did not produce central neurotoxicity.

  • Racecadotril demonstrates intestinal antisecretory activity in vivo
    Alimentary Pharmacology & Therapeutics, 1999
    Co-Authors: M P Primi, L Bueno, P Baumer, H Berard, Jeannemarie Lecomte
    Abstract:

    Background Racecadotril (acetorphan), a potent enkephalinase inhibitor, protects endogenous enkephalins from degradation. Racecadotril exhibits experimental and clinical antidiarrhoeal activity without any effect on intestinal motility, suggesting selective antisecretory activity. The antisecretory effect of Racecadotril was directly assessed in the present study. Methods A 1 m, jejunal, Thiry–Vella loop was created in six mongrel dogs, and water and ionic fluxes were evaluated during infusion (2 mL/min) of Tyrode solution labelled with 14C-polyethylene glycol. Fluxes were determined both in the basal state and 5–6 h after commencement of a 2-h infusion of cholera toxin (0.4 μg/mL). Racecadotril (10 mg/kg) or vehicle was given orally with and without prior intravenous administration of naloxone (0.1 mg/kg) or phentolamine (0.2 mg/kg). Results Basal absorption remained unchanged following Racecadotril administration; however, Racecadotril significantly decreased (P = 0.01) cholera toxin-induced water, sodium, and potassium hypersecretion, from 0.73 ± 0.15 to 0.37 ± 0.13 mL/min; from 125.0 ± 16.1 to 14.7 ± 9.5 μMol/min; and from 3.41 ± 0.66 to 1.66 ± 0.61 μMol/min, respectively. This antisecretory activity of Racecadotril was suppressed by naloxone but not by phentolamine. Conclusions This study directly demonstrates the antisecretory activity of Racecadotril in relation to the protection of endogenous enkephalins.

  • Racecadotril versus placebo in the treatment of acute diarrhoea in adults
    Alimentary Pharmacology & Therapeutics, 1999
    Co-Authors: H Hamza, P Baumer, H Berard, Ben H Khalifa, Jeannemarie Lecomte
    Abstract:

    Methods A two-centre, double-blind, parallel-group, randomized study was carried out to compare the efficacy and tolerability of Racecadotril (100 mg three times daily) and placebo in 70 adult patients with acute diarrhoea. An objective criterion of antisecretory activity, stool weight, was used. Results Racecadotril produced a significant (P = 0.025) decrease in stool weight during the first day of treatment compared with placebo, and was also associated with significantly fewer diarrhoeic stools than placebo after 1 day of treatment (P = 0.027). Racecadotril and placebo were equally well tolerated, and the frequency of symptoms and signs was similar in both groups after 4 days of treatment. Fewer patients on Racecadotril suffered from abdominal distension following treatment (5.6% vs. 18.2% on placebo). Conclusions Racecadotril acts rapidly to resolve acute diarrhoea and has an incidence of adverse events similar to that of placebo.

  • comparison of Racecadotril and loperamide in children with acute diarrhoea
    Alimentary Pharmacology & Therapeutics, 1999
    Co-Authors: D Turck, H Berard, N Fretault, Jeannemarie Lecomte
    Abstract:

    Methods A multicentre, randomized, double-blind, double-placebo, parallel-group study was carried out to compare the efficacy, tolerability, and safety of Racecadotril (100 mg three times daily) and loperamide (2 mg after each diarrhoeic stool) in 157 adults with acute diarrhoea. Patients were treated for 7 days or until recovery, if this took place earlier. Results Both groups of patients passed similar numbers (mean ± S.E.M.) of stools before recovery (3.5 ± 0.5 for Racecadotril vs. 2.9 ± 0.4 for loperamide), and the duration of diarrhoea (mean ± S.E.M.) was similar in both groups (14.9 ± 2.0 h for Racecadotril and 13.7 ± 2.2 h for loperamide). Both treatments reduced the incidence of associated symptoms and signs during the study, and both were similarly well tolerated. However, more patients on loperamide reported rebound constipation during treatment (18.7% vs. 9.8% with Racecadotril). Conclusions The enkephalinase inhibitor, Racecadotril, and the intestinal transit inhibitor, loperamide, were similarly and rapidly effective in resolving the symptoms and associated signs of diarrhoea.

Giovambattista De Sarro - One of the best experts on this subject based on the ideXlab platform.

Martin C Michel - One of the best experts on this subject based on the ideXlab platform.

  • sa1790 comparative clinical studies between Racecadotril and loperamide or saccharomyces boulardii in adult patients with acute diarrhea
    Gastroenterology, 2015
    Co-Authors: Manuel Plomer, Tobias Mueck, Thomas Weiser, Harald Weigmann, Martin C Michel
    Abstract:

    that oral HBB has a fast onset of action, and relief of cramping gastrointestinal pain can be expected as early as 15 min after intake of 20 mg HBB (=two Buscopan® tablets). REF: 1Schaefer E, Ewe K (1990) Fortschr Med 108 (25), 488; 2Mueller-Lissner S et al. (2006) Aliment Pharmacol Ther 23, 1741; 3Ge Z et al. (2011) Int J Clin Pharmacol Ther 49 (3), 198; 4Lacy BE et al. (2013) Scand J Gastroenterol 48 (8), 926; 5Mueller-Lissner S et al. (2011) Pharmacol Pharm 2, 82

  • a comprehensive review of the pharmacodynamics pharmacokinetics and clinical effects of the neutral endopeptidase inhibitor Racecadotril
    Frontiers in Pharmacology, 2012
    Co-Authors: Marion Eberlin, Tobias Muck, Martin C Michel
    Abstract:

    Racecadotril, via its active metabolite thiorphan, is an inhibitor of the enzyme neutral endopeptidase (NEP, EC 3.4.24.11), thereby increasing exposure to NEP substrates including enkephalins and atrial natriuretic peptide (ANP). Upon oral administration Racecadotril is rapidly and effectively converted into the active metabolite thiorphan, which does not cross the blood–brain-barrier. Racecadotril has mainly been tested in animal models and patients of three therapeutic areas. As an analgesic the effects of Racecadotril across animal models were inconsistent. In cardiovascular diseases such as hypertension or congestive heart failure results from animal studies were promising, probably related to increased exposure to ANP, but clinical results have not shown substantial therapeutic benefit over existing treatment options in cardiovascular disease. In contrast, Racecadotril was consistently effective in animal models and patients with various forms of acute diarrhea by inhibiting pathologic (but not basal) secretion from the gut without changing gastro-intestinal transit time or motility. This included studies in both adults and children. In direct comparative studies with loperamide in adults and children, Racecadotril was at least as effective but exhibited fewer adverse events in most studies, particularly less rebound constipation. Several guidelines recommend the use of Racecadotril as addition to oral rehydration treatment in children with acute diarrhea.

  • A comprehensive review of the pharmacodynamics, pharmacokinetics and clinical effects of the neutral endopeptidase inhibitor Racecadotril
    Frontiers Media S.A., 2012
    Co-Authors: Marion Eeberlin, Thomas Emück, Martin C Michel
    Abstract:

    Racecadotril, via its active metabolite thiorphan, is an inhibitor of the enzyme neutral endopeptidase (NEP, EC 3.4.24.11), thereby increasing exposure to NEP including enkephalins and atrial natriuretic peptide. Upon oral administration Racecadotril is rapidly and effectively converted into the active metabolite thiorphan, which does not cross the blood-brain-barrier. Racecadotril has mainly been tested in animal models and patients of three therapeutic areas. As an analgesic the effects of Racecadotril across animal models were inconsistent. In cardiovascular diseases such as hypertension or congestive heart failure results from animal studies were promising, probably related to increased exposure to atrial natriuretic peptide, but clinical results have not shown substantial therapeutic benefit over existing treatment options in cardiovascular disease. In contrast, Racecadotril was consistently effective in animal models and patients with various forms of acute diarrhea by inhibiting pathologic (but not basal) secretion from the gut without changing gastro-intestinal transit time or motility. This included studies in both adults and children. In direct comparative studies with loperamide in adults and children, Racecadotril was at least as effective but exhibited fewer adverse events in most studies, particularly less rebound constipation. Several guidelines recommend the use of Racecadotril as addition to oral rehydration treatment in children with acute diarrhea

Mohamed Kamel - One of the best experts on this subject based on the ideXlab platform.

  • application of high performance thin layer chromatographic method for simultaneous determination of co formulated ofloxacin and Racecadotril in their oral dosage form
    Journal of Advanced Pharmacy Research, 2020
    Co-Authors: Fathy M Salama, Nasr M Elabasawi, Ahmed Elolemy, Mohamed A Hasan, Mohamed Kamel
    Abstract:

    Objectives: This study aimed to develop and validate a simple, rapid, economical, precise and accurate HPTLC method for simultaneous determination of ofloxacin and Racecadotril has been developed. Methods: Chromatographic separation was achieved using silica gel aluminum plate 60 F254 (10*10) as a stationary phase and dichloromethane: methanol: tri-ethylamine (95:5:0.1 by volume) as a mobile phase. The developed plates scanned densitometrically using UV detector. Detection was carried out at 254 nm over the concentration range of 100-800 ng/spot for ofloxacin and 30-240 ng/spot for Racecadotril. The Rf value of ofloxacin and Racecadotril was found to be 0.15 and 0.85 respectively. Results: The method is validated for different validation parameter such as linearity, accuracy, precision, LOD, LOQ and robustness and the result were found to be within the acceptance limit as per the guideline of international conference on harmonization (ICH). Conclusion: The described TLC-densitometric method was successfully applied to simultaneous determination of ofloxacin and Racecadotril in their pure forms and pharmaceutical dosage form without previous separation.

  • application of high performance liquid chromatographic method for simultaneous determination of Racecadotril and ofloxacin in their pharmaceutical dosage form
    Al-Azhar Journal of Pharmaceutical Sciences, 2019
    Co-Authors: Mohamed Kamel
    Abstract:

    Racecadotril and ofloxacin are co-formulated for treatment of acute symptomatic diarrhea. In the present work RP-HPLC method was developed for simultaneous determination of Racecadotril and ofloxacin in the combined dosage form. An isocratic separation was carried out on BDS Equisil  C18 (150 X 4.6 mm, 5 μm particle size) reversed phase column with a mobile phase consists of water and acetonitrile in the ratio of (20:80 % v/v) and pH 3 maintained by 0.1% ortho phosphoric acid. The flow rate was 1 ml/min and UV detection at 230 nm. The linear regression analysis of the calibration graphs showed a good linear relationship over a concentration range of 5-25 μg/ml with main recovery percent 100.06±0.952 and 99.93±0.798 for Racecadotril and ofloxacin, respectively. The proposed method was validated according to ICH guidelines, and has been successfully applied for simultaneous determination of both drugs in both bulk and commercial dosage form.

Marion Eberlin - One of the best experts on this subject based on the ideXlab platform.

  • Racecadotril in the treatment of acute diarrhea in children a systematic comprehensive review and meta analysis of randomized controlled trials
    BMC Pediatrics, 2018
    Co-Authors: Marion Eberlin, Tobias Mueck, Min Chen, Jan Dabritz
    Abstract:

    Racecadotril is a guideline-recommended option for the treatment of acute diarrhea in children but existing guidelines and previous reviews of the field are based on a small fraction of published evidence. Therefore, we have performed a systematic search for randomized controlled trials evaluating Racecadotril as add-on or in comparison to other treatments. A search was performed in PubMed, Scopus and Google Scholar without limits about country of origin or reporting language. A meta-analysis was conducted for the five most frequently used efficacy parameters. We have retrieved 58 trials, from nine countries including six in comparison to placebo, 15 in comparison to various active treatments and 41 as add-on to various standard treatments (some multi-armed studies allowing more than one comparison). Trials used 45 distinct efficacy parameters, most often time to cure, % of cured children after 3 days of treatment, global efficacy and number of stools on second day of treatment. Racecadotril was superior to comparator treatments in outpatients and hospitalized patients with a high degree of consistency as confirmed by meta-analysis for the five most frequently used outcome parameters. For instance, it reduced time to cure from 106.2 h to 78.2 h (mean reduction 28.0 h; P < 0.0001 in 24 studies reporting on this parameter). Tolerability of Racecadotril was comparable to that of placebo (10.4% vs. 10.6% adverse events incidence) or that of active comparator treatments other than loperamide (2.4% in both groups). Based on a comprehensive review of the existing evidence, we conclude that Racecadotril is more efficacious than other treatments except for loperamide and has a tolerability similar to placebo and better than loperamide. These findings support the use of Racecadotril in the treatment of acute diarrhea in children.

  • Racecadotril in the treatment of acute diarrhea in children: a systematic, comprehensive review and meta-analysis of randomized controlled trials
    'Springer Science and Business Media LLC', 2018
    Co-Authors: Marion Eberlin, Tobias Mueck, Min Chen, Jan Dabritz
    Abstract:

    Abstract Background Racecadotril is a guideline-recommended option for the treatment of acute diarrhea in children but existing guidelines and previous reviews of the field are based on a small fraction of published evidence. Therefore, we have performed a systematic search for randomized controlled trials evaluating Racecadotril as add-on or in comparison to other treatments. Methods A search was performed in PubMed, Scopus and Google Scholar without limits about country of origin or reporting language. A meta-analysis was conducted for the five most frequently used efficacy parameters. Results We have retrieved 58 trials, from nine countries including six in comparison to placebo, 15 in comparison to various active treatments and 41 as add-on to various standard treatments (some multi-armed studies allowing more than one comparison). Trials used 45 distinct efficacy parameters, most often time to cure, % of cured children after 3 days of treatment, global efficacy and number of stools on second day of treatment. Racecadotril was superior to comparator treatments in outpatients and hospitalized patients with a high degree of consistency as confirmed by meta-analysis for the five most frequently used outcome parameters. For instance, it reduced time to cure from 106.2 h to 78.2 h (mean reduction 28.0 h; P 

  • a comprehensive comparison of the efficacy and tolerability of Racecadotril with other treatments of acute diarrhea in adults
    Frontiers of Medicine in China, 2016
    Co-Authors: Wolfgang Fischbach, Viola Andresen, Marion Eberlin, Tobias Mueck, Peter Layer
    Abstract:

    Racecadotril is a guideline-recommended treatment to alleviate symptoms of acute diarrhea. A systematic review of randomized studies was performed comparing efficacy and safety of treatment with Racecadotril to that with placebo or active treatments in adults. In five double-blind studies, Racecadotril and placebo had comparable tolerability but Racecadotril was more effective. This was consistent across multiple efficacy parameters including duration of diarrhea, number of diarrheic stools, abdominal pain and meteorism; it was also consistent across countries in Africa, Asia and Europe. In six randomized studies in outpatients comparing Racecadotril to loperamide, resolution of symptoms occurred with similar speed and efficacy; however, Racecadotril treatment was associated with less rebound constipation and less abdominal discomfort. A seventh comparative study performed in geriatric nursing home residents reported a superior efficacy of Racecadotril. In direct comparison with Saccharomyces boulardii treatment, Racecadotril exhibited similar tolerability but was more efficacious. One study compared Racecadotril to octreotide in patients with acute diarrhea requiring hospitalization, rehydration and antibiotic treatment; in this cohort, octreotide was more efficacious than Racecadotril. In conclusion, in adults with acute diarrhea Racecadotril is more efficacious than placebo or Saccharomyces boulardii, similarly efficacious as loperamide and, in patients with moderate to severe disease as add-on to antibiotics, less than octreotide. The tolerability of Racecadotril is similar to that of placebo or Saccharomyces boulardii and better than that of loperamide, particularly with regard to risk of rebound constipation. Taken together these data demonstrate that Racecadotril is a suitable treatment to alleviate symptoms of acute diarrhea in adults.

  • a comprehensive review of the pharmacodynamics pharmacokinetics and clinical effects of the neutral endopeptidase inhibitor Racecadotril
    Frontiers in Pharmacology, 2012
    Co-Authors: Marion Eberlin, Tobias Muck, Martin C Michel
    Abstract:

    Racecadotril, via its active metabolite thiorphan, is an inhibitor of the enzyme neutral endopeptidase (NEP, EC 3.4.24.11), thereby increasing exposure to NEP substrates including enkephalins and atrial natriuretic peptide (ANP). Upon oral administration Racecadotril is rapidly and effectively converted into the active metabolite thiorphan, which does not cross the blood–brain-barrier. Racecadotril has mainly been tested in animal models and patients of three therapeutic areas. As an analgesic the effects of Racecadotril across animal models were inconsistent. In cardiovascular diseases such as hypertension or congestive heart failure results from animal studies were promising, probably related to increased exposure to ANP, but clinical results have not shown substantial therapeutic benefit over existing treatment options in cardiovascular disease. In contrast, Racecadotril was consistently effective in animal models and patients with various forms of acute diarrhea by inhibiting pathologic (but not basal) secretion from the gut without changing gastro-intestinal transit time or motility. This included studies in both adults and children. In direct comparative studies with loperamide in adults and children, Racecadotril was at least as effective but exhibited fewer adverse events in most studies, particularly less rebound constipation. Several guidelines recommend the use of Racecadotril as addition to oral rehydration treatment in children with acute diarrhea.

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