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

Abstract

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 mu g/mL, 053 +/- 0.20 mu g/mL, 2.10 +/- 0.30 hours, 2.00 +/- 0.00 hours, 2.94 +/- 0.13 mu g h/mL, 2.84 +/- 0.25 mu g h/mL, and 3.16 +/- 0.19 mu g h/mL, 3.10 +/- 0.14 mu g h/mL, respectively. In addition, 90% Cls 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 (R) RTU 5% CEF in cattle.