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

Abstract

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 a "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 considerably 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.

Formulation and development of orodispersible sustained release tablet of domperidone

“…Domperidone is known to undergo rapid and complete absorption from gut 57,58 . The drug plasma concentration declined rapidly thereafter with no drug being detected beyond 8 h. Domperidone undergoes rapid first pass metabolism though renal clearance is low 59 .…”

Safety and Efficacy of Galactogogues: Substances that Induce, Maintain and Increase Breast Milk Production

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The Control of Cancer Chemotherapy-Induced Nausea and Vomiting

“…Trials are now urgently needed to establish optimal oral and rectal dosing schedules against a variety of emetogenic chemotherapy regimes. The low drug bioavailability from the oral and rectal preparations (84) may mean that large doses will be needed to suppress emesis resulting from C T Z stimulation. Present data indicate that dosing with rectal suppositories appears most efficacious (43), but dosing should commence at least 4 h prior to chemotherapy (84).…”