INTEREST in the possible causal relationship of disorders of lipid metabolism to development of atherosclerosis, particularly coronary artery disease, has stimulated the search for agents which can normalize serum lipid levels with few undesirable symptoms and no toxic effects.
A mixture of clofibrate (ethyl p-chlorophenoxyisobutyrate) and androsterone (Atromid) was synthesized in 1962 by Thorp and Waring 1 and made available for oral administration in the form of 250 mg capsules each containing 2.5 mg clofibrate and 5.5 mg of androsterone.
The mode of action of this mixture has not been established. Thorp 2 suggested that the chlorophenoxyisobutyrate anion displaces serum albumin-bound acidic substrates, coenzymes, or hormones and that the effects of the displaced acids are predominantly localized in the liver, causing a reduction in lipid synthesis. Further investigation has demonstrated that the effective compound is clofibrate unaided by the addition of androsterone in combination.3-5
This compound has been