The effect of broad-spectrum antibiotics on warfarin excretion and metabolism in the rat

Journal Article · Tue Dec 01 04:00:00 EST 1981 · Res. Commun. Chem. Pathol. Pharmacol.; (United States)

OSTI ID:5439889

Remmel, R P; Elmer, G W

The excretion and metabolism of /sup 14/C-warfarin in rats was examined in a crossover experiment, the first phase consisting of treatment with normal saline, the second phase using the same animals given neomycin, bacitracin, and tetracycline orally. Urine and feces were collected every 24 hours for 72 hours and examined for warfarin and its metabolites, both unconjugated and conjugated. Significantly more radioactivity was eliminated in th feces of antibiotic-treated rats. The feces of antibiotic-treated rats contained only trace amounts of beta-glucuronidase activity. Urine contained a similar ratio of unconjugated to conjugated radioactivity in both treatment groups, but the antibiotic-treated animals had significantly larger amount of conjugates in their feces. Examination of metabolic profiles of conjugated and unconjugated fractions revealed significantly fewer hydroxylated metabolites in antibiotic-treated rats, especially in the feces. The lower amount of hydroxylative metabolism in attributed to a reduction in gut flora-medicated interohepatic recycling caused by the antibiotics.

• Research Organization: Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle
• OSTI ID: 5439889
• Journal Information: Res. Commun. Chem. Pathol. Pharmacol.; (United States), Journal Name: Res. Commun. Chem. Pathol. Pharmacol.; (United States) Vol. 34:3; ISSN RCOCB
• Country of Publication: United States
• Language: English

Related Subjects

550201 -- Biochemistry-- 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
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BIOLOGICAL WASTES
BODY FLUIDS
CARBON 14 COMPOUNDS
CLEARANCE
COUMARIN
DRUGS
ESTERS
EXCRETION
FECES
HETEROCYCLIC COMPOUNDS
LABELLED COMPOUNDS
LACTONES
MAMMALS
MATERIALS
METABOLISM
METABOLITES
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PESTICIDES
PYRANS
RATS
RODENTS
SENSITIVITY
URINE
VERTEBRATES
WASTES