title: Dose determination and confirmation of a long-acting formulation of ceftiofur (ceftiofur crystalline free acid) administered subcutaneously for the treatment of bovine respiratory disease.
abstract: The objective of this work was to determine and confirm an effective dose of ceftiofur crystalline free acid sterile oil suspension (CCFA-SS, 100 mg ceftiofur equivalents (CE)/mL], a long-acting single-administration ceftiofur formulation, for the treatment of the bacterial component of bovine respiratory disease (BRD). Study 1 was a dose determination study that used an intratracheal Mannheimia haemolytica (Pasteurella haemolytica) challenge model to evaluate single-administration doses of CCFA-SS at 0.0, 1.1, 2.2, 3.3, 4.4 or 5.5 mg CE/kg body weight (BW) for the treatment of BRD. Data from this study were used to select doses for field testing in three multi-location clinical studies. In Study 2, the efficacy of a single administration dose of CCFA-SS at 4.4 mg CE/kg BW was compared with a negative control for the treatment of naturally occurring BRD in feedlot cattle. Treatments were administered when uniform clinical signs of BRD were present. Study 3 used a design similar to Study 2, and compared single-administration doses of CCFA-SS at 3.0 or 4.4 mg CE/kg BW with the positive-control tilmicosin (Micotil(R) 300 Injection, Elanco Animal Health) at 10 mg/kg BW. Study 4 compared the efficacy of single doses of CCFA-SS of 1.1-8.8 mg CE/kg BW with tilmicosin at 10 mg/kg BW. A total of 1176 cattle were included in these clinical studies. In Study 1, a dose of 4.55 mg CE/kg BW was determined to be effective. This was rounded to 4.4 mg CE/kg for field testing. In Study 2, a single dose of CCFA-SS at 4.4 mg CE/kg BW had a higher treatment success rate on day 14 (61%) than negative controls (26%, P < 0.01). However, in Study 3 this dose was judged to be at the beginning of an efficacious dose range for the treatment of BRD when compared with tilmicosin. In Study 4, day 28 treatment success rates were higher for CCFA-SS at 4.4-8.8 CE/kg BW than for tilmicosin (P=0.002) or the noneffective CCFA-SS dose of 1.1 mg CE/kg BW (P < 0.001). Based on decision criteria for Study 4, the effective dose was determined to be 4.4-5.5 mg CE/kg BW. These clinical studies demonstrated that a single dose of CCFA-SS (100 mg CE/mL) administered subcutaneously (s.c.) in the neck at 4.4-5.5 mg CE/kg BW is an effective treatment for BRD in feedlot cattle. However, this route of administration is no longer being considered for this formulation because of the ceftiofur residues that are present at the injection site for extended periods of time.
authors.affiliation: Pharmacia Animal Health, Kalamazoo, MI 49001, USA. beth.hibbard@pharmacia.com
authors.forename: B
authors.initials: B
authors.lastname: Hibbard
authors.forename: E J
authors.initials: EJ
authors.lastname: Robb
authors.forename: S T
authors.initials: ST
authors.lastname: Chester
authors.forename: K J
authors.initials: KJ
authors.lastname: Dame
authors.forename: J F
authors.initials: JF
authors.lastname: Boucher
authors.forename: G R
authors.initials: GR
authors.lastname: Alaniz
mesh_terms: D000818:Animals; D002417:Cattle; D002511:Cephalosporins / Q000008:administration & dosage* / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D005260:Female; D007279:Injections, Subcutaneous / Q000662:veterinary; D008297:Male; D016978:Mannheimia haemolytica / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008923:Missouri; D009333:Neck; D012766:Pasteurellosis, Pneumonic / Q000188:drug therapy*
chemical_list: D002511:Cephalosporins; C053503:ceftiofur