Assessment of ruminal degradation, oral bioavailability, and toxic effects of anticoagulant rodenticides in sheep

Objective-To assess the rate and extent of ruminal degradation of warfarin, chlorophacinone, and bromadiolone in vitro and determine the oral availability and clinical and hemostatic effects of each anticoagulant rodenticide in adult sheep. Animals-3 Texel sheep. Procedure-Samples of ruminal fluid were incubated with each of the anticoagulants to assess the kinetics of ruminal degradation over 24 hours. To determine the plasma kinetics of the anticoagulants, each sheep received each of the anticoagulants IV or via a rumen implanted cannula at 2-month intervals (3 rodenticide exposures/sheep). At intervals during a 240- to 360 hour period after treatment, prothrombin time (PT) was measured, plasma anticoagulant concentration was assessed, and clinical signs of rodenticide poisoning were monitored. In plasma and rumen extracts, anticoagulant concentrations were determined via high-performance liquid chromatography. Results-In the rumen extracts, anticoagulants were slightly degraded (< 15%) over 24 hours. In vivo, oral availability of warfarin, chlorophacinone, and bromadiolone was estimated at 79%, 92%, and 88%, respectively. Although maximum PT was 80 seconds after chlorophacinone and bromadiolone treatments, no clinical signs of toxicosis were detected; PT returned to baseline values within 2 weeks. Conclusions and Clinical Relevance-In sheep, warfarin, chlorophacinone, and bromadiolone were not degraded in the rumen but their bioavailabilities were high after oral administration; the kinetics of these compounds in sheep and other mammals are quite similar. These data suggest that the lack of susceptibility of ruminants to these anticoagulant rodenticides cannot be explained by either ruminal degradation or the specific toxicokinetics of these anticoagulants.