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Domperidone | Pharmacology

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Domperidone | Pharmacology
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Domperidone | Dosing
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Action(s)

    

Centrally Acting Antiemetic and Prokinetic


Dopamine-2 Antagonist; antagonizes dopamine in the GI tract and chemoreceptor trigger zone. Domperidone increases lower oesophageal sphincter  pressure. A similar mechanism of action to Metoclopramide, but with fewer adverse CNS effects as it doesn't pass through the blood-brain barrier.


  • Anti-emetic: Treatment of vomiting.

  • Prokinetic/Gastrokinetic: Used in small herbivores with gut stasis.  

  • Stimulation of lactation: May be used to stimulate milk production in horses and small animals.

Dose Information

    

Mechanism of Action(s)

    

Peripheral Actions


  • Dopamine Antagonist: Anti-emetic properties, active in the CTZ and GI tract

  • Alpha1 and Beta Antagonist: Active in the stomach

    

Metabolism

    

Hepatic Metabolism


  • Mechanism: Domperidone undergoes rapid and extensive hepatic metabolism by hydroxylation and N-dealkylation.  

  • Pathway: CYP3A4 is a major form of cytochrome P-450 involved in the N-dealkylation of Domperidone, whereas CYP3A4, CYP1A2 and CYP2E1 are involved in Domperidone aromatic hydroxylation.

    

Elimination

    

Mixed Biliary and Urinary Excretion


  • Metabolites: Metabolites are excreted in the faeces and urine.

    

Evidence Base

    

  1. Ahmad, N., Keith-Ferris, J., Gooden, E., Abell, T., 2006. Making a case for domperidone in the treatment of gastrointestinal motility disorders. Curr Opin Pharmacol 6, 571–576. https://doi.org/10.1016/j.coph.2006.07.004

  2. Al-Khamis, K.I., Kaka, J.S., Matar, K.M., 1987. Effect of domperidone on cimetidine and ranitidine absorption in rabbits. Biopharm Drug Dispos 8, 319–325. https://doi.org/10.1002/bdd.2510080403

  3. Barone, J.A., 1999. Domperidone: a peripherally acting dopamine2-receptor antagonist. Ann Pharmacother 33, 429–440. https://doi.org/10.1345/aph.18003

  4. Champion, M.C., Hartnett, M., Yen, M., 1986. Domperidone, a new dopamine antagonist. CMAJ 135, 457–461.

  5. Delpierre, S., Peyrot, J., Guillot, C., Grimaud, C., 1985. Ventilatory effects of domperidone, a new dopamine antagonist, in anaesthetized rabbits. Arch Int Pharmacodyn Ther 275, 47–58.

  6. Doggrell, S.A., Hancox, J.C., 2014. Cardiac safety concerns for domperidone, an antiemetic and prokinetic, and galactogogue medicine. Expert Opin Drug Saf 13, 131–138. https://doi.org/10.1517/14740338.2014.851193

  7. Frommeyer, G., Fischer, C., Ellermann, C., Lange, P.S., Dechering, D.G., Kochhäuser, S., Fehr, M., Eckardt, L., 2017. Severe Proarrhythmic Potential of the Antiemetic Agents Ondansetron and Domperidone. Cardiovasc. Toxicol. 17, 451–457. https://doi.org/10.1007/s12012-017-9403-5

  8. Haans, J.J.L., Masclee, A. a. M., 2007. Review article: The diagnosis and management of gastroparesis. Aliment. Pharmacol. Ther. 26 Suppl 2, 37–46. https://doi.org/10.1111/j.1365-2036.2007.03534.x

  9. Hofmeyr, G.J., van Iddekinge, B., 1983. Domperidone and lactation. Lancet 1, 647. https://doi.org/10.1016/s0140-6736(83)91818-4

  10. Kilbinger, H., Weihrauch, T.R., 1982. Drugs increasing gastrointestinal motility. Pharmacology 25, 61–72. https://doi.org/10.1159/000137725

  11. Leeser, J., Bateman, D.N., 1985. Domperidone. Br Med J (Clin Res Ed) 290, 241.

  12. Li, C., Qian, W., Hou, X., 2009. Effect of Four Medications Associated with Gastrointestinal Motility on Oddi Sphincter in the Rabbit. Pancreatology 9, 615–620. https://doi.org/10.1159/000212095

  13. Madisch, A., Vinson, B.R., Abdel-Aziz, H., Kelber, O., Nieber, K., Kraft, K., Storr, M., 2017. Modulation of gastrointestinal motility beyond metoclopramide and domperidone : Pharmacological and clinical evidence for phytotherapy in functional gastrointestinal disorders. Wien Med Wochenschr 167, 160–168. https://doi.org/10.1007/s10354-017-0557-3

  14. Mt-Isa, S., Tomlin, S., Sutcliffe, A., Underwood, M., Williamson, P., Croft, N.M., Ashby, D., 2015. Prokinetics prescribing in paediatrics: evidence on cisapride, domperidone, and metoclopramide. J. Pediatr. Gastroenterol. Nutr. 60, 508–514. https://doi.org/10.1097/MPG.0000000000000657

  15. Oosterveld, W.J., 1981. Vestibular pharmacology of domperidone in rabbits and man. ORL J Otorhinolaryngol Relat Spec 43, 175–180. https://doi.org/10.1159/000275537

  16. Patterson, D., Abell, T., Rothstein, R., Koch, K., Barnett, J., 1999. A double-blind multicenter comparison of domperidone and metoclopramide in the treatment of diabetic patients with symptoms of gastroparesis. Am. J. Gastroenterol. 94, 1230–1234. https://doi.org/10.1111/j.1572-0241.1999.00456.x

  17. Phan, H., DeReese, A., Day, A.J., Carvalho, M., 2014. The dual role of domperidone in gastroparesis and lactation. Int J Pharm Compd 18, 203–207.

  18. Reddymasu, S.C., Soykan, I., McCallum, R.W., 2007. Domperidone: review of pharmacology and clinical applications in gastroenterology. Am J Gastroenterol 102, 2036–2045. https://doi.org/10.1111/j.1572-0241.2007.01255.x

  19. Robinson, P., 2008. Dosage and drug interactions of domperidone. Am J Gastroenterol 103, 1049. https://doi.org/10.1111/j.1572-0241.2007.01772_12.x

  20. Schapira, M., Henrion, J., Heller, F.R., 1990. The current status of gastric prokinetic drugs. Acta Gastroenterol. Belg. 53, 446–457.

  21. Smolina, K., Mintzes, B., Hanley, G.E., Oberlander, T.F., Morgan, S.G., 2016. The association between domperidone and ventricular arrhythmia in the postpartum period. Pharmacoepidemiol Drug Saf 25, 1210–1214. https://doi.org/10.1002/pds.4035

  22. Templeton, I., Ravenstijn, P., Sensenhauser, C., Snoeys, J., 2016. A physiologically based pharmacokinetic modeling approach to predict drug-drug interactions between domperidone and inhibitors of CYP3A4. Biopharm Drug Dispos 37, 15–27. https://doi.org/10.1002/bdd.1992

  23. Valenzuela, J.E., Dooley, C.P., 1984. Dopamine antagonists in the upper gastrointestinal tract. Scand J Gastroenterol Suppl 96, 127–136.

  24. van Roeden, S.E., Belle-van Meerkerk, G., van Tuyl, S.A.C.B., van de Ree, M.A., Muller, A.F., 2013. [Domperidone and the risk of sudden cardiac death]. Ned Tijdschr Geneeskd 157, A6770.

  25. Wauquier, A., Niemegeers, C.J., Janssen, P.A., 1981. Neuropharmacological comparison between domperidone and metoclopramide. Jpn J Pharmacol 31, 305–314. https://doi.org/10.1254/jjp.31.305

    

Validation

    


Phase 1 Author(s)

*McArthur, S .D.J. MRCVS  (01/04/2022)

  1. Data: Primary Data

  2. User Interface: Primary Data

  3. Evidence Grade: Primary Grade (Scale)

  4. Efficacy Rating: Primary Rating (Colour)


Phase 1 Analyst(s)


Invitation Analyst 1: Contribution is welcomed.

  • No invitation analysis is available at present


Phase 2 Analyst(s)


Community Analyst 1:  Contribution is welcomed.

  • No content analysis is available at present


    

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