Dissociation of increased lauric acid omega-hydroxylase activity from the antilipidemic action of clofibrate.

Clofibrate, an antilipidemic drug that acts by a still obscure mechanism, is known to specifically increase up to 30-fold the activity of the hepatic cytochrome P-450 isozyme that omega-hydroxlates lauric acid. The thesis that accelerated catabolism of medium-length fatty acids initiated by omega-hydroxylation contributes significantly to the antilipidemic action of clofibrate has been examined by measuring the impact on serum triglyceride levels of coadministering clofibrate and a suicide substrate that inactivates the hydroxylase. The results suggest that the antilipidemic action of clofibrate does not depend critically on the enhanced omega-hydroxylation of fatty acids.