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 Vd(ss) was 0.2 +/- 0.06 L/kg, the mean volume of distribution by the area method Vd(area) was 0.38 +/- 0.22 L/kg, mean residence time (MRT) was 6.5 +/- 1.8 h, mean residence time in peripheral tissues (MRTp) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Whittem
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Department of Veterinary Clinical Sciences, Massey University, Palmerston North, New Zealand.
Freeman
D A
DA
Hanlon
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Parton
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K
D000704:Analysis of Variance; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D002417:Cattle; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous / Q000662:veterinary; D017136:Ion Transport / Q000187:drug effects; D011339:Probenecid / Q000008:administration & dosage / Q000494:pharmacology*; D014018:Tissue Distribution
D002511:Cephalosporins; C053503:ceftiofur; D011339:Probenecid; D001241:Aspirin