THE EFFECTS ON THE PHARMACOKINETICS OF INTRAVENOUS CEFTIOFUR SODIUM IN DAIRY-CATTLE OF SIMULTANEOUS INTRAVENOUS ACETYL SALICYLATE (ASPIRIN) OR PROBENECID

Ceftiofur sodium is a third-generation cephalosporin antibiotic. It is possible that non-steroidal anti-inflammatory drugs such as acetyl salicylate (aspirin) may be used concomitantly with ceftiofur sodium in dairy cattle. Therefore this study evaluated potential pharmacokinetic interactions between ceftiofur sodium and aspirin. In addition, this study evaluated the potential for interaction between ceftiofur and its active metabolites and the organic anion transporter. The organic anion transporter substrate used in this evaluation was probenecid. Ten healthy, non-pregnant, non-lactating dairy cows were used in a randomized complete three-way crossover design. In repeated experiments all cows were administered: (1) 2 mg of ceftiofur sodium per kg body weight by intravenous bolus or (2) 10 mg of probenecid per kg body weight by intravenous bolus, followed immediately by 2 mg of ceftiofur sodium per kg body weight by intravenous bolus or (3) 26 mg of aspirin per kg body weight by intravenous bolus, followed immediately by 2 mg of ceftiofur sodium per kg body weight by intravenous bolus. For treatment with ceftiofur sodium alone, the mean volume of distribution at steady-state V-d(ss) was 0.2 +/- 0.06 L/kg, the mean volume of distribution by the area method V-d(area) was 0.38 +/- 0.22 L/kg, mean residence time (MRT) was 6.5 +/- 1.8 h, mean residence time in peripheral tissues (MRT(p)) was 2.6 +/- 1.0 h, total body clearance (Cl) was 0.032 +/- 0.013 L/kg/h and elimination rate constant (beta) was 0.097 +/- 0.044 h(-1) (mean +/- standard deviation). No statistically significant changes were detected as a result of preceding treatment with aspirin. Preceding treatment with probenecid resulted in a decrease in both Cl (0.007 +/- 0.005 L/kg/h) and MRT(p) (0.89 +/- 0.45 h). These results suggest that ceftiofur or its metabolites may interact with the organic anion transporter, but that consideration of alterations to dose and dose interval may not be necessary when ceftiofur sodium is administered to the cow concomitantly with a single dose of aspirin.