Bioequivalence Study of Two Different Formulations of Ceftiofur Following Intramuscular Administration in Cattle

The aim of the present study was to explore the bioequivalence of ceftiofur hydrochloride sterile suspension (5%) in two formulations, a reference formulation (Excenel® Ready To Use (RTU) 5% Ceftiofur (CEF) (Pfizer, New Jersey, USA)) and a test formulation (ceftipure 5% (Alke, Istanbul, Turkey)). Both products were administered to each of 10 healthy Holstein cattle (1.1 mg/kg body weight, intramuscularly) during a two-period crossover parallel experimental design. Blood samples were collected before and at 0.16, 0.33, 0.5, 1, 2, 4, 8, 12, and 24 hours after a single intramuscular administration. The plasma concentrations of ceftiofur and desfuroylceftiofur-related metabolites were measured by high-performance liquid chromatography. The descriptive pharmacokinetic parameters were calculated and compared by variance analysis, with 90% confidence intervals. The comparison values between reference and test formulation for maximum plasma concentration, time to maximum concentration, area under the plasma concentration-time curve to last concentration, and area under the plasma concentration-time curve extrapolated to infinity were 0.59 ± 0.15 µg/mL, 0.53 ± 0.20 µg/mL, 2.10 ± 0.30 hours, 2.00 ± 0.00 hours, 2.94 ± 0.13 µg h/mL, 2.84 ± 0.25 µg h/mL, and 3.16 ± 0.19 µg h/mL, 3.10 ± 0.14 µg h/mL, respectively. In addition, 90% CIs of these ratios for reference and test product were within acceptable ranges, and the relative bioavailability (F) of test products was 96.57% according to area under the plasma concentration-time curve to last concentration. The results demonstrated that ceftipure 5% is bioequivalent to Excenel®RTU 5% CEF in cattle.

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