RT Journal Article
SR Electronic
T1 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.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 696
OP 702
VO 19
IS 3
A1 T F Woolf
A1 S M Bjorge
A1 A E Black
A1 A Holmes
A1 T Chang
YR 1991
UL http://dmd.aspetjournals.org/content/19/3/696.abstract
AB 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.