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

A transdermal patch was developed to circumvent the emesis associated with the oral and intravenous administration of a dopamine agonist, qu inelorane, to dogs. Approximate steady-state plasma concentrations wer e 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 t ransdermal patch. At steady-state conditions, dogs received either a s ingle 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 radioacti ve free base, C-14-quinelorane, applied to their abdomens for 24 hours ; the approximate dose was 0.18 mg/kg. The plasma pharmacokinetics wer e measured by liquid scintillation counting and ELISA. The systemic bi oavailability of quinelorane, as measured by the ELISA, was 30%, indic ative of first-pass metabolism. The radioactive urinary metabolite pro file was similar for all three routes of administration. Principal ent ities in the urine were quinelorane, the N-despropyl- and the hydroxy- lactam- metabolites, accounting for 29, 25 and 3% of the dose, respect ively. The major route of excretion of radioactivity was via the urine , irrespective of the route by which the drug was administered.