DISPOSITION OF C-14 QUINELORANE IN DOGS FOLLOWING ORAL OR INTRAVENOUS DOSING AND TRANSDERMAL, PATCH APPLICATION

A transdermal patch was developed to circumvent the emesis associated with the oral and intravenous administration of a dopamine agonist, quinelorane, to dogs. Approximate steady-state plasma concentrations were achieved following the daily application of a transdermal patch for 7 days. Each dog received between 0.1 and 0.2 mg/kg per day from the transdermal patch. At steady-state conditions, dogs received either a single oral dose of C-14-quinelorane at 0.1 mg/kg, a bolus intravenous dose of 0.03 mg/kg or had a transdermal patch containing the radioactive free base, C-14-quinelorane, applied to their abdomens for 24 hours; the approximate dose was 0.18 mg/kg. The plasma pharmacokinetics were measured by liquid scintillation counting and ELISA. The systemic bioavailability of quinelorane, as measured by the ELISA, was 30%, indicative of first-pass metabolism. The radioactive urinary metabolite profile was similar for all three routes of administration. Principal entities in the urine were quinelorane, the N-despropyl- and the hydroxy-lactam- metabolites, accounting for 29, 25 and 3% of the dose, respectively. The major route of excretion of radioactivity was via the urine, irrespective of the route by which the drug was administered.