Resflor (R) is a fixed combination of two active ingredients: florfenicol and flunixin. The purpose of this study was to document the bioequivalence of two routes of administration namely the test intramuscular (IM) and the reference subcutaneous (SC) route of administration in cattle. Ten healthy female cattle were randomly allocated to one of the two groups of a two-period crossover design with a washout interval of 15 or 16 days between the two periods. The tested doses for the two routes of administration were 40 mg/kg BW for florfenicol and 2.2 mg/kg BW for flunixin. Blood samples were regularly collected up to 5 days following administration. Florfenicol and flunixin were assayed using HPLC analytical techniques. The limits of quantification (LOQ) were 0.05 mu g/mL and 0.012 mu g/mL for florfenicol and flunixin respectively allowing quantifying florfenicol plasma concentrations over 5 days and flunixin plasma concentrations over 24-58h post administration. Based on the regulatory criterion requiring that the 90% confidence interval of the ratio of the two pivotal pharmacokinetic parameters for florfenicol (AUC and Cmax) needs to be totally included in an a priori equivalence interval of +/- 20%, it was concluded that the two routes of administration cannot be considered as bioequivalent. Indeed, the mean differences were as high as 35% and 63% for the AUC and Cmax respectively, the IM route administration leading to higher florfenicol exposure than the reference SC route of administration. In contrast, the kinetic disposition of flunixin was rather similar for the two routes of administration.
