Role of metabolism in furazolidone pharmacokinetics

Thesis/Dissertation · Tue Jan 01 04:00:00 EST 1985

OSTI ID:6704223

Kotun, R J

The pharmacokinetics of the antimicrobial, /sup 14/C-furazolidone (N-(5-nitro-2-furfurylidene)-3-amino-2-oxazolidinone), in the male Wistar rat was defined and related to the agent's in vitro bacterial and hepatic metabolism. The parmacokinetic profiles after intravenous and oral administration (5 mg/kg) were deemed irregular because of the presence of transient rises in blood levels of the drug over time. The drug was also rapidly cleared from the body. Within 48 hours, 100% of the total administered radioactivity was excreted. Approximately 90% was excreted in the urine and 10% was excreted in the feces. The irregular profiles were not attributable to metabolism by the blood enzymes. Incubation of the drug in rat blood for 2 hours did not result in any significant degradation of the drug. The irregular profiles were not due to enterohepatic recirculation. The kinetics profiles were still irregular after catheterizing the bile duct and no furazolidone was detected in the bile. Metabolism of /sup 14/C-furazolidone in microsomal and cytosolic fractions of rat liver was very rapid. Maximum metabolism was achieved within five minutes. Pretreating the rats or the incubates with unlabelled furazolidone increased the rate and extent of metabolism. In microsomes, addition of allopurinol as a pretreatment decreased the production of polar metabolites. In the cytosol, addition of allopurinol to the incubate as a pretreatment resulted in an increased production of lipophilic metabolites. Pretreating the rats with allopurinol resulted in inconsistent findings in the in vitro metabolism.

• Research Organization: Pittsburgh Univ., PA (USA)
• OSTI ID: 6704223
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIMICROBIAL AGENTS
BACTERIA
BLOOD-PLASMA CLEARANCE
BODY
CARBON 14 COMPOUNDS
CLEARANCE
DIGESTIVE SYSTEM
DRUGS
DYNAMIC FUNCTION STUDIES
ESCHERICHIA COLI
GLANDS
IN VIVO
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
MAMMALS
METABOLISM
MICROORGANISMS
ORGANS
RATS
RODENTS
TRACER TECHNIQUES
VERTEBRATES