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 i ts potential for use in the therapy of newborn calf infections due to gram-negative bacteria. The minimum inhibitory concentrations of cefix ime for 90% (MIC(90)) of field isolates of Escherichia coli, Salmonell a and Pasteurella were 0.10-0.40 mu g/mL. The serum disposition kineti cs of cefixime following intravenous and oral administration was evalu ated. 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 pr oteins. Oral absorption was comparatively slow and bioavailability val ues for single 5 mg/kg doses were 20.2% after the administration of 20 0 mg of cefixime in capsules, 28.3% after dosing an aqueous solution o f cefixime and 35.7% after fasted calves received the solution of cefi xime. Mean serum drug concentrations 12 h after the cefixime solution was administered orally (5 mg/kg) were 1.05 mu g/mL for the milk-fed c alves and 1.76 mu g/mL; for the fasted calves. Computations showed tha t mean free drug concentrations equal to the MIC(50) of the drug for g ram-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.