Tissue distribution of /sup 14/C-diazepam and its metabolites in rats

Journal Article · · Drug Metab. Dispos.; (United States)

OSTI ID:6252143

Igari, Y; Sugiyama, Y; Sawada, Y; Iga, T; Hanano, M

We have kinetically investigated the tissue distribution of /sup 14/C-diazepam and described the appearance and disappearance of its metabolites (3-hydroxydiazepam, desmethyldiazepam, and oxazepam) following a single iv injection of /sup 14/C-diazepam into rats. Significant amounts of oxazepam were detected in plasma and various tissues in the rat, contrary to previous reports. Concentration-time profiles of diazepam in the main disposing organs (liver, kidney, and lung) and the other organs (brain, heart, and small intestine) indicated that diazepam was distributed rapidly to these organs. Concentration-time profiles of diazepam in the main tissues for drug distribution (skin and adipose) indicated that diazepam was slowly distributed to these tissues, whereas that in muscle, which is also responsible for drug distribution, indicated that diazepam was less rapidly distributed to this tissue. Metabolites appeared in plasma and various tissues or organs immediately after iv injection of diazepam. Metabolites levels in plasma and various tissues or organs were significantly lower than that of diazepam except for liver and small intestine, where metabolites levels were higher compared to that of diazepam and metabolites exhibited a considerable persistence.

• Research Organization: Faculty of Pharmaceutical Sciences, University of Tokyo, Japan
• OSTI ID: 6252143
• Journal Information: Drug Metab. Dispos.; (United States), Journal Name: Drug Metab. Dispos.; (United States) Vol. 10:6; ISSN DMDSA
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
CARBON 14 COMPOUNDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DISTRIBUTION
DRUGS
HYPNOTICS AND SEDATIVES
INJECTION
INTAKE
INTRAVENOUS INJECTION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
METABOLITES
PHARMACOLOGY
RATS
RODENTS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
VERTEBRATES