Racecadotril

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Racecadotril
Clinical data
Trade namesHidrasec, Tiorfan, Zedott, others
Other namesBenzyl 2-[3-(acetylthio)-2-benzylpropanamido]acetate
AHFS/Drugs.comInternational Drug Names
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
  • EU: Rx-only[1]
Pharmacokinetic data
Protein binding90% (active metabolite thiorphan)[2]
MetabolismLiver-mediated[2]
Onset of action30 min
Elimination half-life3 hours[2]
ExcretionUrine (81.4%), feces (8%)[2]
Identifiers
  • (RS)-Benzyl N-[3-(acetylthio)-2-benzylpropanoyl]glycinate
JSmol)
ChiralityRacemic mixture
Melting point89 °C (192 °F)
  • CC(=O)SCC(CC1=CC=CC=C1)C(=O)NCC(=O)OCC2=CC=CC=C2
  • InChI=1S/C21H23NO4S/c1-16(23)27-15-19(12-17-8-4-2-5-9-17)21(25)22-13-20(24)26-14-18-10-6-3-7-11-18/h2-11,19H,12-15H2,1H3,(H,22,25) ☒N
  • Key:ODUOJXZPIYUATO-UHFFFAOYSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Racecadotril, also known as acetorphan, is an

electrolytes into the intestine.[3] It is available in France (where it was first introduced in ~1990) and other European countries (including Germany, Italy, the United Kingdom, Spain, Portugal, Poland, Finland, Russia and the Czech Republic) as well as most of South America and some South East Asian countries (including China, India and Thailand), but not in the United States. It is sold under the tradename Hidrasec, among others.[4] Thiorphan is the active metabolite of racecadotril, which exerts the bulk of its inhibitory actions on enkephalinases.[5]

Medical uses

Racecadotril is used for the treatment of acute diarrhea in children and adults and has better tolerability than loperamide, as it causes less constipation and flatulence.[6][7] Several guidelines have recommended racecadotril use in addition to oral rehydration treatment in children with acute diarrhea.[8]

Contraindications

Racecadotril has no contraindications apart from known hypersensitivity to the substance.[9][10]

There is insufficient data for the therapy of chronic diarrhea, for patients with

saccharase deficiency, as it contains sugar.[7][9]

Side effects

The most common adverse effect is headache, which occurs in 1–2% of patients.

urticaria, angioedema, erythema multiforme, and erythema nodosum.[9][10]

Overdose

No cases of overdose are known. Adults have tolerated 20-fold therapeutic doses without ill effects.[10]

Interactions

No interactions in humans have been described. Combining racecadotril with an ACE inhibitor can theoretically increase the risk for angioedema.[9][10]

Racecadotril and its main metabolites neither inhibit nor

pharmacokinetic
interactions.

Pharmacology

Mechanism of action

Enkephalins are peptides produced by the body that act on opioid receptors with preference for the δ subtype.[11] Activation of δ receptors inhibits the enzyme adenylyl cyclase, decreasing intracellular levels of the messenger molecule cAMP.[7]

The

nM, protecting enkephalins from being broken down by these enzymes. (Racecadotril itself is much less potent at 4500 nM.)[7][8] This reduces diarrhea related hypersecretion in the small intestine without influencing basal secretion. Racecadotril also has no influence on the time substances, bacteria or virus particles stay in the intestine.[10]

Pharmacokinetics

Some metabolites of racecadotril.
top left: precursor to the active metabolite
top right: active metabolite
bottom row: inactive metabolites

Racecadotril is rapidly absorbed after oral administration and reaches

elimination half-life, measured from enkephalinase inhibition, is three hours.[7][8][9]

Thiorphan is further metabolized to inactive metabolites such as the methyl

thioether and the methyl sulfoxide. Both active and inactive metabolites are excreted, mostly via the kidney (81.4%), and to a lesser extent via the feces (8%).[10]

Society and culture

Brand names

In France, Portugal and Spain it is sold as Tiorfan and in Italy as Tiorfix. In India it is available as Redotril and Enuff.[4]

See also

References

  1. ^ "Active substance: racecadotril" (PDF). List of nationally authorised medicinal products. European Medicines Agency. 26 November 2020.
  2. ^ a b c d "SPC-DOC_PL 39418-0003.PDF" (PDF). Medicines and Healthcare Products Regulatory Agency. Bioprojet Europe Ltd. 26 December 2012. Retrieved 7 May 2014.
  3. ^
    PMID 10804038
    .
  4. ^ a b Brayfield A, ed. (13 December 2013). "Racecadotril". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 6 May 2014.
  5. PMID 3015640
    .
  6. PMID 27790616
    .
  7. ^
    ISBN 978-3-7741-9846-3
    .
  8. ^
    PMID 22661949
    .
  9. ^ a b c d e Mediq.ch: racecadotril. Accessed 2019-12-30.
  10. ^ a b c d e f g Haberfeld H, ed. (2019). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Hidrasec 100 mg-Hartkapseln.
  11. PMID 31752279
    .

External links

  • "Racecadotril". Drug Information Portal. U.S. National Library of Medicine.
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