Pharmacokinetic fate of 14C-labeled deoxynivalenol in swine

Abstract

The pharmacokinetics of the trichothecene mycotoxin deoxynivalenol (DON) was investigated in swine following intravenous (0.30 mg, 0.35 microCi/kg) and intragastric (0.60 mg, 0.60 microCi/kg) administration of the 14C-labeled toxin. After iv dosing, plasma concentration data favored a three-compartment open model with half-life values for the rapid distribution (alpha), slower distribution (beta), and terminal elimination (gamma) phases of 5.8, 96.7, and 510.0 min, respectively. The apparent volume of distribution (V'd) was 1.34 liter/kg, the volume of the central compartment (Vc) was 0.166 liter/kg, and the plasma clearance was 1.81 ml/min/kg. DON was rapidly cleared essentially unchanged (greater than 95%), and was excreted primarily in urine (86-104%), with minor elimination in bile (3-5%). Following intragastric dosing DON was very rapidly absorbed, reaching near peak plasma levels within 15-30 min. Levels remained elevated (63-325 ng/ml) for approximately 9 hr, and began declining slowly (t1/2 beta = 7.1 hr) thereafter. The calculated systemic bioavailability (F) was between 48 and 65%, although urinary and biliary recoveries indicated marginally greater absorption actually occurred (54-85%). Overall, although DON was eliminated rapidly and completely within 24 hr following a single iv or intragastric dose, data suggest that residues may undergo temporary sequestration in a tissue depot.