Summary
The pharmacokinetics and bioavailability of domperidone, a novel gastrokinetic, were studied in healthy male subjects by comparing plasma concentrations and urinary excretion following intravenous, intramuscular, oral and rectal administration. Two oral dosage forms were studied: 10-mg tablets and a 10-mg/ml oral solution. The influence of a meal on the oral bioavailability and the dose-proportionality were also investigated.
Plasma levels of intravenous domperidone could be described by a three-compartment model with a rapid distribution of 40% of the dose to as «shallow» peripheral compartment. The final elimination half-life was 7.5 hours. Peak plasma levels were reached within 30 minutes following intramuscular and oral administration and at 1–4 hours following rectal administration. Since domperidone showed an extensive first-pass elimination, AUC-values -a measure for the bioavailability- were consider-ably lower after oral than after parenteral administration. Equal oral and rectal doses gave a similar bioavailability. AUC-values increased proportionally with the dose over a 10–60 mg range. Cumulative urinary excretion of unchanged domperidone was proportional to corresponding AUC-values.
The bioavailability was discussed in the light of the therapeutic results.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Niemegeers C.J.E., Schellekens K.H.L. and Janssen P.A.J. (1980): The antiemetic effects of domperidone, a novel potent gastrokinetic. Archs. int Pharmacodyn.,244, 130–140.
Laduron P.M. and Leysen J.E. (1979): Domperidone, a specificin vitro dopamine antagonist, devoid ofin vivo central dopaminergic activity. Biochem. Pharmac.,28, 2161–2165.
Baudry M., Martres M.P. and Schartz J.C. (1979):3H-Domperidone: a selective ligand for dopamine receptors. Naunyn-Schmiedebergs Arch. Pharmac.,308, 231–237.
Heykants J., Knaeps A., Meuldermans W. and Michiels M. (1981): On the pharmacokinetics of domperidone in animals and man. I. Plasma levels of domperidone in rats and dogs. Age-related absorption and passage through the blood-brain barrier in rats. Europ. J. Drug Metab. Pharmacokin. (this issue).
Michiels M., Hendriks R. and Heykants J. (1981): On the pharmacokinetics of domperidone in animals and man. II. Tissue distribution, placental and milk transfer of domperidone in the Wistar rat. Europ. J. Drug Metab. Pharmacokin. (this issue).
Van Nueten J.M., Ennis C., Helsen L., Laduron P.M. and Janssen P.A.J. (1978): Inhibition of dopamine receptors in the stomach: an explanation of the gastrokinetic properties of domperidone. Life Sci.,23, 453–458.
Van Nueten J.M. and Janssen P.A.J. (1979): Effect of domperidone on gastric relaxation caused by dopamine, secretin, 5-hydroxytryptamine, substance P and adenosine triphosphate, 7th Int. Symposium on Gastrointestinal Motility, Iowa City.
Van Nueten J.M. (1980): Is dopamine an inhibitory modulator of gastric motility? TIPS, 233–235.
Reyntjens A.J., Niemegeers C.J.E., Van Nueten J.M., Laduron P., Heykants J., Schellekens K.H.L., Marsboom R., Jagenau A., Broekaert A. and Janssen P.A.J. (1978): Domperidone, a novel and safe gastrokinetic anti-nauseant for the treatment of dyspepsia and vomiting. A survey of pharmacological and clinical results. Arzneimittel-Forsch.,28, 1194–1196.
Broekaert A. (1979): Effect of domperidone on gastric emptying and secretion. Post-grad. med. J.,55, (Suppl. 1), 11–14.
Platteborse R. (1979): The effect of domperidone on pyloric activity in dog and in man. Post-grad. med. J.,55, (Suppl. 1), 15–18.
Weihrauch T.R., Förster C.F. and Krieglstein J. (1979): Evaluation of the effect of domperidone on human oesophageal and gastroduodenal motility by intraluminal manometry. Post-grad. med. J.,55, (Suppl. 1), 7–10.
Reyntjens A. (1979): Domperidone as an antiemetic; summary of research reports. Post-grad. med. J.,55, (Suppl. 1), 50–54.
Haarmann K., Lebkuchner F., Widmann A., Kief W. and Esslinger M. (1979): A double-blind study of domperidone it the symptomatic treatment of chronic postprandial upper gastrointestinal distress. Post-grad. med. J.,55, (Suppl. 1), 24–27.
Englert W. and Schlich D. (1979): A double-blind crossover trial of domperidone in chronic postprandial dyspepsia. Post-grad. med. J.,55, (Suppl. 1), 28–29.
Bekhti A. and Rutgeerts L. (1979): Domperidone in the treatment of functional dyspepsia in patients with delayed gastric emptying. Post-grad. med. J.,55, (Suppl. 1), 30–32.
Van Outryve M., Lauwers W. and Verbeke S. (1979): Domperidone for the symptomatic treatment of chronic post-prandial nausea and vomiting. Post-grad. med. J.,55, (Suppl. 1), 33–35.
Van Eygen M., Dhondt F., Heck E., Ameryckx L. and Van Ravensteyn H. (1979): A double-blind comparison of domperidone and metoclopramide suppositories in the treatment of nausea and vomiting in children. Post-grad. med. J.,55, (Suppl. 1), 36–39.
Clara R., Van Hollebeke J. and Heck E. (1979): A multicentre pilot study of parenteral and rectal administration of domperidone in the treatment of severe vomiting in children. Post-grad. med. J.,55, (Suppl. 1), 43–44.
Boulanger M., Dubois A. and Lecron L. (1979): Domperidone in the prevention of post-operative nausea and vomiting. Post-grad. med. J.,55, (Suppl. 1), 45–47.
Meuldermans W., Hurkmans R., Swijsen E., Hendrickx J., Michiels M., Lauwers W. and Heykants J. (1981): On the pharmacokinetics of domperidone in animals and man. III. Comparative study on the excretion and metabolism of domperidone in rats, dogs and man. Europ. J. Drug. Metab. Pharmacokin. (this issue).
Michiels M., Hendriks R. and Heykants J. (1980): A sensitive and specific radioimmunoassay for domperidone. Manuscript in preparation.
Meuldermans W.E.G. and Heykants J.J.P. (1976): The plasma protein binding and distribution of etomidate in dog, rat and human blood. Archs. int. Pharmacodyn.,221, 150–162.
Ehrnebo M., Agurell A., Borëus L.O., Gordon E. and Lönroth U. (1974): Pentazocine binding to blood cells and plasma proteins. Clin. Pharmac. Ther.,16, 424–429.
Gibaldi M. and Perrier D. (1975): Pharmacokinetics, Marcel Dekker, Inc., New York.
Michiels M., Heykants J. and Reyntjens A. (1981): On the pharmacokinetics of domperidone in animals and man. V. Detailed study on the distribution of domperidone in rats and dogs. Europ. J. Drug. Metab. Pharmacokin., (this issue).
Rowland M. (1972): Influence of route of administration on drug availability. J. Pharm. Sci.,61, 70–74.
28. De Boer A.G. (1980): «First-pass» eliminatie van enige «high-clearance» farmaca na rectale toediening aan de mens en de rat. Pharm. Weekblad,115, 613–620.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Heykants, J., Hendriks, R., Meuldermans, W. et al. On the pharmacokinetics of domperidone in animals and man IV. The pharmacokinetics of intravenous domperidone and its bioavailability in man following intramuscular, oral and rectal administration. European Journal of Drug Metabolism and Pharmacokinetics 6, 61–70 (1981). https://doi.org/10.1007/BF03189516
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF03189516