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

There are no refereed controlled documentations of the skeletal analgesic efficacy of different dosages of flunixin meglumine (FM). 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. 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 20 min after lameness induction for 5 h and hourly for another 8 h. 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. Compared to SAL, half-dose FM reduced HR at 2.33, 2.67, 4.0-8.0, and 10.0 h and LS at 1.33-12.0 h (P < 0.05). Single- and double-dose FM reduced HR from 0.67 to 12.0 h and LS from 1.0 to 12.0 h post administration (P < 0.05). Compared with half-dose FM, single- and double-dose LS were further decreased from 1.67 to 12.0 h post administration (P < 0.05). Mean peak and decaying plasma FM concentrations were different between dosages in a dose-dependent manner through 6 h post administration (P < 0.05). 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. 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.