ArticleThe Journal of veterinary medical science2026
An ordinary differential equation-based integrated pharmacokinetic-pharmacodynamic model for predicting anticoagulant responses to warfarin and diphacinone across rodent and bat species.
Article in The Journal of veterinary medical science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Interspecies differences in sensitivity to anticoagulant compounds remain an important issue in veterinary toxicology and wildlife risk assessment. In the present study, we developed an integrated pharmacokinetic-pharmacodynamic (PK/PD) model to quantitatively compare anticoagulant responses between rats and bats, linking hepatic exposure to vitamin K epoxide reductase (VKOR) inhibition and subsequent changes in prothrombin time-international normalized ratio (PT-INR). Species-specific pharmacokinetic parameters were estimated from experimental concentration-time data and incorporated into a mechanistic turnover model describing VKOR activity and clotting factor synthesis. The model reproduced dose-dependent PT-INR prolongation in rats and successfully described the delayed and attenuated anticoagulant responses observed in bats. Sensitivity analyses identified hepatic clearance (CLh), hepatic distribution volume (Vh), and the half-maximal inhibitory concentration for VKOR (IC
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