title: 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.
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000932:Antiemetics / Q000008:administration & dosage / Q000378:metabolism*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000378:metabolism*; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D004294:Domperidone; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000378:metabolism*; D011485:Protein Binding; D012007:Rectum; D013488:Suppositories
chemical_list: D000932:Antiemetics; D001562:Benzimidazoles; D001798:Blood Proteins; D010880:Piperidines; D013488:Suppositories; D004294:Domperidone