Pharmacokinetics of ceftiofur hydrochloride administration in sheep and pharmacokinetic interaction of between both drugs for administration with flunixin meglumine

In this study, it was aimed to determine the pharmacokinetics and bioavailability of desfuroylceftiofur (DFC) following intravenous (IV), intramuscular (IM), and subcutaneous (SC) administrations of 2,2 mg/kg dose of ceftiofur hydrochloride (CFT HCl) to healthy sheep, as well as to determine the pharmacokinetic interaction that may occur between CFT HCI (2,2 mg/kg) and flunixin meglumine (FM) (2,2 mg/kg) after simultaneous IV administration. Six Kıvırcık female sheep (12-14 months old, 37,21±1,70 kg) were used in the study. The study was carried out according to five-period longitudinal pharmacokinetic design. A 2-week washout period was left between administrations. In the first period, CFT HCl solution was administered by IV route, in the second and third periods CFT was used with IM and SC route respectively, in the fourth period FM was used by the IV route, in the fifth period FM and CFT HCl IV solutions were administered separately by IV route. Plasma drug concentrations were measured using high pressure liquid chromatography-UV. The pharmacokinetic parameters of DFC were analyzed using a noncompartmental model and the pharmacokinetic parameters of FM were analyzed using the two-compartment open model. After IV, IM and SC administrations, the elimination half-life (t1/2ʎz) of DFC was similar, while the mean residence time (MRT) was found to be 8,49; 12,87 and 11,73 hours, respectively. The bioavailability of DFC was determined as 70,79% and 79,52% after IM and SC administration, respectively. While AUC0-32, AUC0-∞ values of DFC increased with FM administration, its ClT decreased significantly (P<0,05). In simultaneous administration of FM with CFT, while t1/2α and V1 values of FM increased, the k12 value decreased significantly (P<0,05). In this study, FM decreased the elimination of DFC while increasing its plasma concentration. CFT was able to provide a %T>MIC value in the range of 50-70% for bacterial isolates with a MIC value of ≤1 µg/mL when CFT was administered at a dose of 2.2 mg/kg, at a dose interval of 24 hours, with IV alone, IM, SC and FM simultaneously. Further studies are needed to determine the pharmacokinetic and pharmacodynamic interaction in the presence of infection. Keywords : Pharmacodynamics, pharmacokinetics, flunixin meglumine, sheep, ceftiofur