Characterization and therapeutic alteration of the biliary excretion and enterohepatic cycling of zearalenone in sexually immature swine

Thesis/Dissertation · Sun Jan 01 04:00:00 EST 1989

OSTI ID:5613728

Biehl, M L

The purposes of these studies were to characterize the biliary excretion and enterohepatic cycling (EHC) of zearlenone (ZEN) in young pigs and to therapeutically mimic the effect of bile removal in enhancing body clearance of ZEN. ({sup 3}H)ZEN was administered intravenously (IV), orally, and intravenous with bile removal (IVB) to female, 10- to 14-week old pigs. The biological half of total plasma radioactivity in IV and orally dosed pigs (86.6h) was much greater than that of IVB pigs (3.34h). Secondary peaks in plasma metabolite concentrations were seen during the terminal elimination phase in IV and oral animals and metabolites were still detectable at 48h postdosing. In IVB pigs, these peaks were absent, relative metabolite profiles were altered and ZEN and metabolites were no longer detectable after 16 hrs. Biliary recovery of radioactivity, principally as glucuronide conjugates was extensive (45.61 {plus minus} 4.73%) and significantly greater than that of fecal recovery in IV (6.56 {plus minus} 0.78%) or oral (21.74 {plus minus} 1.56%) pigs. Absorption of ZEN from the intestinal tract was estimated to be 80-85%. Intraduodenal administration of bile containing ({sup 3}H)ZEN and glucuronide metabolites resulted in recovery of 64.5 {plus minus} 4.89% of the dose in bile, 20.78 {plus minus} 3.94% in urine, and the presence of glucuronide conjugates of ZEN and {alpha}-zearalenol (ZEL) in portal and jugular plasma. Evidence for metabolism of ZEN by the intestinal mucosa was present. A pharmacokinetic compartmental model for the disposition of intravenously administered ZEN and metabolites in swine is proposed. The mean terminal elimination rate and corresponding biological half life for ZEN in IV pigs was 0.03h{sup {minus}1} and 28.97h, respectively, and for IVB pigs 0.24h {sup {minus}1} and 2.94h.

• Research Organization: Illinois Univ., Urbana, IL (USA)
• OSTI ID: 5613728
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ABSORPTION
ANIMALS
BENZOIC ACID
BIOLOGICAL HALF-LIFE
CARBOXYLIC ACIDS
CLEARANCE
DOMESTIC ANIMALS
EXCRETION
HYDROGEN COMPOUNDS
INJECTION
INTAKE
INTESTINAL ABSORPTION
INTRAVENOUS INJECTION
ISOTOPE APPLICATIONS
MAMMALS
MATHEMATICAL MODELS
METABOLISM
METABOLITES
MONOCARBOXYLIC ACIDS
ORAL ADMINISTRATION
ORGANIC ACIDS
ORGANIC COMPOUNDS
SWINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
UPTAKE
VERTEBRATES