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Journal of Pharmacology And Experimental Therapeutics, Vol. 167, Issue 1, 91-97, 1969
Copyright © 1969 by American Society for Pharmacology and Experimental Therapeutics

THE METABOLISM OF TOLBUTAMIDE IN RAT LIVER

HUEY G. McDANIEL 1, HELEN PODGAINY 1, and RUBIN BRESSLER 1

1 Departments of Medicine and Physiology and Pharmacology, Duke University, Durham, North Carolina

Incubation of tritiumlabeled tolbutamide with a 9000x g rat liver supernatant resulted in a conversion to metabolically inactive carboxytolbutamide. The incubation of tolbutamide with rat liver microsomes resulted in the formation of hydroxytolbutamide. This conversion was inhibited by SKF 525-A. The oxidation of hydroxytolbutamide was carried out by the rat liver 100,000 x g supernatant. Alcohol dehydrogenase also catalyzed the oxidation of hydroxytolbutamide, and the product of this reaction was oxidized by both xanthine oxidase and aldehyde dehydrogenase. Carboxytolbutamide was formed from the oxidation of hydroxytolbutamide catalyzed by alcohol dehydrogenase and aldehyde dehydrogenase.

Submitted on December 27, 1967
Accepted on January 10, 1969






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