Metabolism of the acyl-CoA:cholesterol acyltransferase inhibitor 2,2-dimethyl-N- (2,4,6-trimethoxyphenyl) dodecanamide in rat and monkey. Omega-/beta-oxidation pathway
Woolf, T.F.; Bjorge, S.M.; Black, A.E.; Holmes, A.; Chang, T.
Drug Metabolism and Disposition the Biological Fate of Chemicals 19(3): 696-702
1991
ISSN/ISBN: 0090-9556 PMID: 1680639 Document Number: 370321
2,2-Dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide (CI-976) is a newly developed hypocholesterolemic agent. In pharmacokinetic studies, CI-976 was found to have a much shorter elimination half-life in monkey (0.6 hr) compared to rat (8 hr). Radioactivity analysis of biological samples from rats and monkeys administered [14C]CI-976 either iv or orally showed CI-976 to be extensively metabolized to a single major common metabolite. This metabolite was isolated and its structure determined by GC/MS, LC/MS, and NMR spectroscopy as a 6-carbon chain-shortened carboxylic acid derivative, 5,5-dimethyl-6-oxo-6-[(2,4,6-trimethoxyphenyl)amino]-hexanoic acid. A potential pathway leading to this carboxylic acid derivative may involve initial omega-oxidation followed by beta-oxidation. A potential species difference in omega-/beta-oxidative biotransformation capabilities appears to exist.