Metabolism and excretion of a new 5-lipoxygenase inhibitor in rats, guinea-pigs, beagles and rhesus monkeys

Abstract

1. The 5-lipoxygenase inhibitor (I), a substituted benzothiazole, is metabolized mainly by glucuronide and/or sulphate conjugation in rat, guinea-pig, beagle and rhesus monkey. Glucuronidation is the major pathway, and sulphation is more extensive in rat and beagle than in guinea-pig and rhesus monkey.

2. After a single oral dosing of ¹⁴C-I (10mg/kg), more than 96% of the dose was excreted in 7 days in all four species, however there is species difference in urinary excretion, which was 2.8 + 0.3% in rat, 46.9.1.6% in guinea-pig, 2.6% in beagle and 68.2% in rhesus monkey.

3. After a single i.v. dose of ¹⁴C-I to bile duct-cannulated rats and guinea pigs, bile was a major route of elimination, and in rats the ratio of glucuronide to sulphate in excreta increased from 0.71.0.01 to 0.93.0.05 as the dose was increased from 0.2 to 20mg/kg.