Clinical pharmacology of cefixime in unweaned calves

Cefixime is a unique third‐generation oral cephalosporin. Its in vitro activity and pharmacokinetic properties have been studied to assess its potential for use in the therapy of newborn calf infections due to gram‐negative bacteria. The minimum inhibitory concentrations of cefixime for 90% (MIC₅₀) of field isolates of Escherichia coli. Salmonella and Pasteurella were 0.10–0.40 μg/mL. The serum disposition kinetics of cefixime following intravenous and oral administration was evaluated. The elimination half‐life of cefixime after intravenous and oral administration was 3.5–4.0 h, the steady‐state volume of distribution was 0.34 L/kg and approximately 90% of the drug was bound to serum proteins. Oral absorption was comparatively slow and bioavailability values for single 5 mg/kg doses were 20.2% after the administration of 200 mg of cefixime in capsules, 28.3% after dosing an aqueous solution of cefixime and 35.7% after fasted calves received the solution of cefixime. Mean serum drug concentrations 12 h after the cefixime solution was administered orally (5 mg/kg) were 1.05 μg/mL for the milk‐fed calves and 1.76 μg/mL for the fasted calves. Computations showed that mean free drug concentrations equal to the MIC₅₀ of the drug for gram‐negative pathogens associated with newborn calf infections can be maintained in tissues by multiple treatments at 5 mg/kg every 12 h or 10 mg/kg every 24 h.