Penetration of Ceftiofur into Sterile versus Mannheimia Haemolytica-Infected Tissue Chambers in Beef Calves after Subcutaneous Administration of Ceftiofur Crystalline Free Acid Sterile Suspension in the Ear Pinna

Abstract

Ceftiofur is a third-generation cephalosporin approved in the US for the treatment of bovine respiratory disease in beef and dairy cattle. Ceftiofur crystalline free acid sterile suspension (CCFA-SS) is a single administration product developed as an extension to the ceftiofur product line. The efficacy of a single dose of CCFA-SS administered subcutaneously in the neck was established in several clinical field studies. However, this route of administration was not acceptable for registration because of extended residues at the injection site. Consequently, the middle third of the posterior aspect of the ear pinna was selected as an alternative site of administration, and pilot studies were conducted to investigate the duration of efficacy resulting from a high concentration formulation. These studies indicated that administration of3.0 mg CE/lb (6.6 mg CE/kg) was efficacious, suggesting that therapeutic concentrations of ceftiofur and its active metabolite, desfuroylceftiofur, were maintained in interstitial fluids at sites of infection for prolonged periods. Bacterial infections of soft tissues, such as the lung, cause interstitial fluid composition changes which may affect the distribution of antibacterials or their in vitro activity in the target tissue. Evaluation of drug concentrations in intersitial fluid poses significant sampling difficulties; however, several studies have employed perforated tissue chambers implanted subcutaneously to characterize interstitial fluid drug concentrations in cattle.

The objectives of this study were to evaluate the plasma and tissue chamber fluid pharmacokinetics of ceftiofur and desfuroylceftiofur after subcutaneous administration of CCFA-SS in the ear pinnae of healthy feedlot calves, and to compare the penetration of ceftiofur and related metabolites into sterile versus Mannheimia haemolyica infected tissue chambers.