Abstract
A hydroxy metabolite of glutethimide (4-hydroxy-2-ethyl-2-phenylglutarimide) was isolated from the acid-hydrolyzed urine of dogs given large doses of glutethimide. Mass spectrometry showed that this metabolite was identical to the metabolite which accumulates to high levels in the plasma of humans intoxicated with glutethimide. The structure of the metabolite was confirmed by nuclear magnetic resonance, mass spectrometry, and infrared analysis. The ED50 for drug-induced ataxia (rotarod test) in mice was 24 mg/kg for the isolated metabolite compared to 47 mg/kg for glutethimide. The results indicate that a hydroxy metabolite which accumulates in the plasma of persons intoxicated with glutethimide possesses significant biological activity. Therefore, this metabolite may contribute to the toxicity of glutethimide in humans.
Footnotes
- Received November 7, 1973.
- Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics
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IDENTIFICATION AND ACTIVITY OF THE HYDROXY METABOLITE THAT ACCUMULATES IN THE PLASMA OF HUMANS INTOXICATED WITH GLUTETHIMIDE
