© 1988 Oxford University Press
research-article |
Pharmacokinetic Fate of14C-Labeled Deoxynivalenol in Swine 1
*Animal Research Centre Ottawa, Ontario, Canada KIA OC6
Plant Research Centre, Agriculture Canada, Central ExperimentalFarm Ottawa, Ontario, Canada KIA OC6
Received April 7, 1987; accepted August 24, 1987
Pharmacokinetic Fate of 14C-Labeled Deoxynivalenol in Swine. PRELUSKY, D. B., HARTIN, K. E., TRENHOLM, H. L., AND MILLER, J. D. (1988). Fundam. Appl Toxicol. 10,276-286. The pharmacokinetics of the trichothecene mycotoxin deoxynivalenol (DON) was investigated in swine following intravenous (0.30 mg, 0.35 µCi/kg) and intragastric (0.60 mg, 0.60 µCi/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 (
), slower distribution (ß), and terminal elimination (
) phases of 5.8, 96.7, and 510.0 min, respectively. The apparent volume of distribution (V') was 1.34 liter/kg, the volume of the central compartment (Kc) was 0.166 liter/kg, and the plasma clearance was 1.81 ml/min/kg. DON was rapidly cleared essentially unchanged (>95%), and was excreted primarily in unne (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 (t ß= 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.