Pharmacokinetic evaluation of ceftiofur in serum, tissue chamber fluid and bronchial secretions from healthy beef-bred calves.
Ceftiofur is a new broad spectrum cephalosporin marketed for the treatment of acute bovine respiratory disease. In this investigation ceftiofur was administered by intramuscular injection, at 24 h intervals, to healthy beef-bred calves for four days at dosages of 2.2 and 4.4 mg/kg of body weight, with 4 wk intervals between dosing regimens. Serum, tissue chamber fluid (TCF), and bronchial secretion (BS) concentrations of ceftiofur were measured by microbiological assay after the first and fourth dose of each dosing regimen. Peak serum concentrations (Cmax) of 8.8 micrograms/mL and 17.3 micrograms/mL were obtained approximately 2 h (Tmax), the time of mean peak concentration) after single injections of 2.2 mg/kg and 4.4 mg/kg, respectively. The Cmax was increased approximately twofold following multiple doses of 2.2 mg/kg (Cmax = 13.1 micrograms/mL) and 4.4 mg/kg (Cmax = 24.1 micrograms/mL). Ceftiofur accumulated slowly into TCF and peak concentrations were found to be approximately 14% of those observed in serum after the first dose and approximately 24% after multiple dosing. Concentrations of ceftiofur in BS were obtained rapidly with peak concentrations reaching 45% of the serum Cmax after the first dose. After multiple dosing the Cmax for BS was approximately 25% of the serum Cmax. This study found that both the 2.2 mg/kg and 4.4 mg/kg dosing regimens resulted in continuous serum, TCF and BS concentrations of ceftiofur that exceeded the minimal concentration required to inhibit the bacteria most frequently isolated from calves with acute bovine respiratory disease.
Halstead
S L
SL
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing 48823.
Walker
R D
RD
Baker
J C
JC
Holland
R E
RE
Stein
G E
GE
Hauptman
J G
JG
D000818:Animals; D001980:Bronchi / Q000378:metabolism*; D002417:Cattle / Q000378:metabolism*; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D015194:Diffusion Chambers, Culture; D006190:Haemophilus / Q000187:drug effects; D006207:Half-Life; D007273:Injections, Intramuscular / Q000662:veterinary; D007442:Intubation, Intratracheal / Q000662:veterinary; D016978:Mannheimia haemolytica / Q000187:drug effects; D016979:Pasteurella multocida / Q000187:drug effects; D014018:Tissue Distribution
D002511:Cephalosporins; C053503:ceftiofur