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

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. ($\sp3$H) ZEN was administered intravenously (IV), orally, and intravenously with bile removal (IVB) to female, 10-to 14-week-old pigs. The biological half life of total plasma radioactivity in IV and orally dosed pigs (86.6 hrs.) was much greater than that of IVB pigs (3.34 hrs.). Secondary peaks in plasma metabolite concentrations were seen during the terminal elimination phase in IV and oral animals and metabolites were still detectable at 48 hrs. 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 $\pm$ 4.73%) and significantly greater than that of fecal recovery in IV (6.56 $\pm$ 0.78%) or oral (21.74 $\pm$ 1.56%) pigs. Absorption of ZEN from the intestinal tract was estimated to be 80-85%. Intraduodenal administration of bile containing ($\sp3$H) ZEN and glucuronide metabolites resulted in recovery of 64.5 $\pm$ 4.89% of the dose in bile, 20.78 $\pm$ 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 0.03 hr$\sp{-1}$ and 28.97 hrs., respectively, and for IVB pigs 0.24 hr$\sp{-1}$ and 2.94 hrs.In another study, oral superactivated charcoal (SAC) altered the disposition of ($\sp3$H) ZEN in swine in a manner similar to total bile removal (EHC interrupted). Glucuronide conjugates were not detectable in plasma after 12 hours with either treatment and fecal recovery of radioactivity in pigs given SAC (30.2 $\pm$ 9.6%) was similar to biliary recovery (32.3 $\pm$ 12.0%) in the other treatment group. 15% dietary alfalfa did not appear to have a significant overall effect.The above findings indicate that biliary excretion and EHC are major factors influencing the disposition of ZEN in pigs and that oral SAC may be therapeutically effective in altering the EHC process.U of I OnlyETDs are only available to UIUC Users without author permissio