Metabolism of afloqualone, a new centrally acting muscle relaxant, in monkeys and dogs

Abstract

The dispositon and metabolism of afloqualone [6-amino-2-fluoromethyl-3-(o-tolyl)-4(3H)-quinazolinone, AFQ] were studied in monkeys and dogs after oral administration of 14C-AFQ. In both species the blood radioactivity reached a maximum 1 to 2 h after the administration, and decreased with apparent half-lives of 3.2 h in the monkey and 7.2 h in the dog. A total of about 90% of the administered radioactivity was recovered from the urine (monkey, 72.3%; dog, 51.8%) and feces (monkey, 19.4%; dog, 36.7%) within 4 or 5 d. AFQ was extensively metabolized in both species. There were species differences in the composition of the urinary metabolites. In the dog, AFQ was monohydroxylated at the 2-,2'-, 3'- and principally 4'-position and each metabolite was further conjugated with glucuronic acid. A'-Acetylated metabolites were not detected. In the monkey, N-acetylation was the main initial step of metabolism followed by hydroxylation at the acetyl-methyl, 2'-methyl and 2-fluoromethyl groups. Phenolic metabolites such as 3'- and 4'-hydroxylated AFQ were not detected. Both animals excreted sulfur-containing metabolites such as the 2-methylthio, 2-methylsulfinyl and 2-methylsulfonyl derivatives of AFQ. © 1983, The Pharmaceutical Society of Japan. All rights reserved.