Depletion and bioavailability of 14C-oxibendazole residues in swine tissues.
Groups of male swine were administered a single oral dose of 14C-oxibendazole in a gelatin capsule at a level of 15 mg kg-1 bodyweight and killed after 10 h, 24 h, and 7 days withdrawal. Combustion analysis indicated that liver was the only tissue which contained significant residues. Owing to the insolubility of oxibendazole, absorption was variable, especially at the early time points. Total residues were highest after 24 h withdrawal (4 ppm) and depleted relatively slowly to approximately 1.8 ppm after 7 days. Extractable residues decreased from 35% to 11% over this same period. When 14C-oxibendazole was fortified into control, lyophilized, pelleted swine liver and fed to rats utilizing the Gallo-Torres model, bioavailability was greater than 94%. In contrast, bioavailability was substantially reduced to approximately 40% when liver containing 14C-oxibendazole residues from dosed swine was fed. This percentage remained constant for liver samples from the 24 h or 7 day withdrawal swine. The date were consistent with the rapid metabolism of oxibendazole and the early formation of a high percentage of bound tissue residues. The significant differences in residue bioavailability and extraction efficiency between the fortified control and dosed tissues indicate that little, if any, parent oxibendazole is present in the dosed tissues, even at early withdrawal times. As non-bioavailable residues are of no toxicological concern, the 60% reduction in bioavailability is significant from a regulatory perspective. The wider safety margin, relative to the established acceptable daily intake (ADI) for oxibendazole, is beneficial to the consumer in terms of human food safety.
Department of Developmental Pharmacokinetics and Drug Metabolism, Pfizer Animal Health, West Chester, PA 19380-1169, USA.
D W
DW
Gottschall
R
R
Wang
D000284:Administration, Oral; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D001682:Biological Availability; D002250:Carbon Radioisotopes; D005506:Food Contamination; D006801:Humans; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism*; D008297:Male; D008460:Meat; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D014018:Tissue Distribution
D000871:Anthelmintics; D001562:Benzimidazoles; D002250:Carbon Radioisotopes; C011321:oxibendazole