title: Pharmacokinetics of a long-acting ceftiofur crystalline-free acid formulation in Asian elephants (Elephas maximus).
abstract: OBJECTIVE
  To determine the pharmacokinetics of a long-acting formulation of ceftiofur, ceftiofur crystalline-free acid (CCFA), following SC injection to Asian elephants (Elephas maximus).
  
  
  METHODS
  11 adult Asian elephants.
  
  
  METHODS
  Each elephant received CCFA (6.6 mg/kg, SC) in the area caudoventral to the base of an ear. Blood samples were collected from an ear vein immediately prior to and at 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours after CCFA administration. Plasma concentrations of desfuroylceftiofur acetamide (the acetamide derivative of ceftiofur) were measured via ultrahigh-pressure liquid chromatography-tandem mass spectrometry. Data were analyzed via a noncompartmental pharmacokinetics approach.
  
  
  RESULTS
  The mean ± SD maximum plasma concentration of desfuroylceftiofur acetamide was 1.36 ± 0.74 μg/mL and was detected at 4718 ± 31.30 hours. The mean ± SD area under the curve from time 0 to infinity was 2278 ± 55.8 μg•h/mL, and the mean residence time from time 0 to infinity was 158.2 ± 90.2 hours. The terminal elimination half-life associated with the slope of the terminal phase had a harmonic mean ± pseudo-SD of 83.36 ± 30.01 hours.
  
  
  CONCLUSIONS
  Elephants tolerated CCFA at a dose of 6.6 mg/kg, SC, well. Dosing recommendations will depend on the mean inhibitory concentration of ceftiofur for each bacterial pathogen. Desfuroylceftiofur acetamide concentrations remained > 0.25 μg/mL for the entire 168-hour study period, which suggested CCFA would provide clinically relevant antimicrobial activity against certain pathogens for 7 to 10 days.
authors.affiliation: Saint Louis Zoo, 1 Government Dr, St Louis, MO 63110, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Adkesson
authors.forename: Randall E
authors.initials: RE
authors.lastname: Junge
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Allender
authors.forename: Tomás
authors.initials: T
authors.lastname: Martín-Jiménez
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004606:Elephants / Q000097:blood / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D007279:Injections, Subcutaneous / Q000662:veterinary; D008297:Male
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C063324:desfuroylceftiofur; C053503:ceftiofur