Metabolites of bromazepam, a benzodiazepine, in the human, dog, rat, and mouse

Morton A. Schwartz, Edward Postma, Stanley J. Kolis, Arthur S. Leon

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The biotransformation of bromazepam, 7‐bromo‐1,3‐dihydro‐5‐(2‐pyridyl)‐2H‐1,4‐benzodiazepin‐2‐one, was studied in four species. Four metabolites were identified and their excretion was quantitatively determined. The major urinary metabolites excreted by three women given single 12‐mg. oral doses of bromazepam‐5‐14C were the conjugated forms of 3‐hydroxybromazepam (I), accounting for 13‐30% of the dose, and 2‐(2‐amino‐5‐bromo‐3‐hydroxybenzoyl)pyridine (IV), accounting for 4‐25% of the dose. Conjugated I was also the major metabolite in three dogs and four groups of mice administered 14C‐bromazepam, but its excretion by four rats was very limited. Together with I, Metabolite IV and 2‐(2‐amino‐5‐bromobenzoyl)pyridine were detected in the excreta of the human, dog, rat, and mouse. Although the pyridyl N‐oxide derivative of bromazepam was not detected as a metabolite in any species, the N4‐oxide was a minor metabolite in dog urine. This is the first reported instance of metabolic N4‐oxidation of a 1,4‐benzodiazepin‐2‐one.

Original languageEnglish (US)
Pages (from-to)1776-1779
Number of pages4
JournalJournal of Pharmaceutical Sciences
Volume62
Issue number11
DOIs
StatePublished - Nov 1973

Keywords

  • Benzodiazepine derivatives—metabolism of bromazepam in human, dog, rat, and mouse, identification of metabolites, mechanisms discussed
  • Biotransfomation—identification of bromazepam metabolites in human, dog, rat, and mouse
  • Bromazepam (a benzodiazepine)—metabolism in human, dog, rat, and mouse, identification of metabolites, mechanisms discussed
  • Metabolites, bromazepam—identified in urine and feces of humans, rats, dogs, and mice

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