Merck + Co., Inc.

Alfred W Alberts

Richard L Monaghan

George E Albers-Schonberg

Carl H Hoffman

Arnold J Repta

Edward M Scolnick

Gregory D Berger

Michael D Greenspan

James D Bergstrom

The instant invention is directed to a method for enhancing the lowering of plasma cholesterol level in a subject in need thereof which comprises the time-controlled administration of a nontoxic therapeutically effective amount of an HMG-CoA reductase inhibitor to said subject which surprisingly affords an equivalent or improved reduction of plasma cholesterol levels while significantly reducing the amount of HMG-CoA reductase inhibitor circulating in the bloodstream of the subject as compared to the same parameters when the oral administration of a conventional rapid release dosage form is utilized.

Method for enhancing the lowering of plasma-cholesterol levels

Compounds of structural formula (I): ##STR1## are squalene synthestase inhibitors useful in inhibiting the biosynthesis of cholesterol in the treatment of hypercholesterolemia and related disorders.

Squalene synthetase inhibitors

Method for enhancing the lowering of plasma cholesterol levels

There is disclosed the use of .beta.-lactone alkylene carboxylic acids and derivatives thereof, which are known compounds, for the use of treating diabetic ketoacidosis. The compounds are administered orally or parenterally and compositions containing the .beta.-lactone alkylene carboxylic acid compounds as the active ingredient are also disclosed.

Treatment of diabetic ketoacidosis

Substances isolated after cultivation of a microorganism belonging to the genus Aspergillus in a culture medium comprise compounds which have structures: ##STR1## Together with salts and esters of the carboxylic acid, these compounds form a class of highly active hypocholesteremic and hypolipemic medicaments.

Hypocholesteremic fermentation products

Substances isolated after cultivation of a microorganism belonging to the genus Aspergillus in a culture medium comprise a compound designated MSD803 which has the lactone structure: ##STR1## as well as its free hydroxy acid form. Together with salts and esters of the free acid form, these compounds form a class of highly active hypocholesteremic and hypolipemic medicaments.

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Princeton, NJ, United States of America

Alfred W Alberts