Metabolic Disposition of Emepronium in the Dog with a Note on the Relationship between Plasma Concentration and Effect

The fate of emepronium (cetiprin®) in the dog has been studied following different routes of administration. The drug is rather extensively metabolized following both intravenous, oral and rectal administration. At least two metabolites are formed. Following intravenous injection twice as much radioactivity is found in the faeces as in the urine, about half in the form of the unchanged drug. This means that there is probably an extensive enterohepatic circulation of the drug. In four dogs 0.6, 0.8, 1.1 and 1.6 % of the dose was excreted unchanged in the urine within 24 hours following oral administration of 20 mg/kg. It is concluded from experiments with the radioactive compound that from 2 to 10 % of the dose is absorbed if metabolism and biliary excretion are taken into account. Plasma concentrations of emepronium in the nanogram range can be determined by gas chromatography of the oxidation product, ben‐zophenone. A plasma concentration of about 20 μ/ml is lethal to both rats and dogs and the threshold concentration for an effect on the heart rate in the dog is about 100 ng/ml.