The effects of phenobarbital induction on the toxicity of brodifacoum in the canine

Abstract

A reliable technique for extraction of brodifacoum (BDF) from serum using ether and ether:acetonitrile [1:1] was developed. Two HPLC systems (A: 1.5% Acetic acid, pH 4.5:acetonitrile [1:2] with 1% dibutylamine and B: 0.2 M Tris, pH 7.5:-acetonitrile [1:3]) were utilized to optimize sensitivity with simultaneous ultraviolet (254 nm & 313 nm) and fluorescent (313 nm excitation with 375 nm emission) detection. The plasma carrier state, and, by inference, the mechanism of brodifacoum absorption were investigated by ultracentrifugation. The description of clinical signs, quantitation of serum BDF concentrations and measurement of laboratory coagulation parameters have simultaneously been examined in experimentally intoxicated dogs. Additionally, the ability to confirm BDF toxicity in a live animal has been established. Further, the presence of BDF in the serum 21 days following an oral LD₅₀ dose suggests that, in dogs receiving significantly greater amounts, clotting factor synthesis may be inhibited for longer periods of time than observed in this study. Coagulation status and brodifacoum kinetics indicated no benefit from phenobarbital induction to dogs poisoned with BDF. Coagulation parameters were unchanged (Activated Coagulation Time) or prolonged (Prothrombin and Proconvertin Time), and BDF kinetics were unchanged (Area Under the Curve) or prolonged (Mean Residence Time) following induction.