Dose titration of the clinical efficacy of intravenously administered flunixin meglumine in a reversible model of equine foot lameness

Reasons for performing study: There are no refereed controlled documentations of the skeletal analgesic efficacy of different dosages of flunixin meglumine (FM). Objectives: The objective of this experiment was to compare the efficacy of various dosages of FM with a negative control. The hypothesis was that higher doses would result in improved efficacy in a dose-dependent manner when tested in a reversible model of foot lameness. Methods: Ten horses shod with adjustable heart bar shoes had weekly modified AAEP grade 4.0/5.0 lameness induced by tightening a set screw against the heart bar. Heart rate (HR) and lameness score (LS) were monitored by one double-blinded investigator at rest; every 20min after lameness induction for 5h and hourly for another 8h. One hour after lameness induction, treatments were administered i.v. in a randomised order: negative control (isotonic saline: SAL) or FM at 0.55 (half-dose), 1.1 (single-dose) or 2.2 (double-dose) mg/kg bwt. Results were compared using RM ANOVA and Student-Newman-Keul's test with the level of significance set at P<0.05. Results: Compared to SAL, half-dose FM reduced HR at 2.33, 2.67, 4.0-8.0, and 10.0h and LS at 1.33-12.0 h (P<0.05). Single- and double-dose FM reduced HR from 0.67 to 12.0h and LS from 1.0 to 12.0h post administration (P<0.05). Compared with half-dose FM, single- and double-dose LS were further decreased from 1.67 to 12.0h post administration (P<0.05). Mean peak and decaying plasma FM concentrations were different between dosages in a dose-dependent manner through 6h post administration (P<0.05). Conclusions: Flunixin meglumine administration affected dependent variables in a dose-dependent manner with half-dose FM clinically effective for a shorter period. Higher dosages did not perform differently from one another. Potential relevance: Practitioners must be aware that half-doses of FM are less efficacious than single doses but double doses are not more efficacious and yet are potentially more toxic.