Disposition of radiolabeled benzoquinolizinyl propionanilide hydrochloride in rats and dogs and identification of several of its metabolites
Leeling, J.L.; Muni, I.A.; Kowalski, T.L.; Johnson, N.
Toxicology and Applied Pharmacology 46(1): 77-85
1978
ISSN/ISBN: 0041-008X PMID: 725952 Document Number: 126208
The biological disposition of 14C-labeled N-(1,3,6,7-hexahydro-11bH-benzo(a)quinolizin-2-yl) propionalide hydrochloride (1), an experimental antihypertensive agent, was studied in the rat and dog. Both species received a single oral dose of [14C]I, 31.6 mg/kg to rats and 6 mg/kg to dogs. The compound was well absorbed by both species. The maximum plasma level of undifferentiated 14C in the dog was nearly equal to that in rat plasma, despite the 5-fold dose difference. Plasma 14C levels in the dog were more persistent: biological half-life estimates (.alpha. phase) were 5.9 and 1 h for the dog and rat, respectively. In the rat the highest tissue 14C concentrations were found in liver and the lowest were found in brain. In both rats and dogs, more than 80% of the administered radioactivity was recovered from feces and urine within 96 h, mostly within the 1st 24 h. The 96 h urinary:fecal excretion ratios of 14C were 35:65 in both species. Metabolic end products of [14C/3H]I (50 mg/kg, rat and 30 mg/kg, dog) were the same in both species. Quantitatively, the rat excreted 2-3 times as much glucuronic acid-conjugated material as the dog.