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% (MIC90) of field isolates of Escherichia coli, Salmonella and Pasteurella were 0.10-0.40 micrograms/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 micrograms/mL for the milk-fed calves and 1.76 micrograms/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.
Ziv
G
G
Ministry of Agriculture, Kimron Veterinary Institute, Bet-Dagan, Israel.
Lavy
E
E
Glickman
A
A
Winkler
M
M
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D002417:Cattle / Q000378:metabolism*; D020682:Cefixime; D002439:Cefotaxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D004304:Dosage Forms; D004926:Escherichia coli / Q000187:drug effects*; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D008657:Metabolic Clearance Rate; D010325:Pasteurella / Q000187:drug effects*; D012015:Reference Standards; D012475:Salmonella / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D004304:Dosage Forms; D020682:Cefixime; D002439:Cefotaxime