title: Plasma and urine disposition and dose proportionality of ceftiofur and metabolites in dogs after subcutaneous administration of ceftiofur sodium.
abstract: Nine male dogs (10.3-13.5 kg body weight) were randomly assigned to three groups of three dogs each and administered ceftiofur sodium subcutaneously as a single dose of 0.22, 2.2, or 4.4 mg ceftiofur free acid equivalents/kg body weight. Plasma and urine samples were collected serially for 72 h and assayed for ceftiofur and metabolites (derivatized to desfuroylceftiofur acetamide) using high-performance liquid chromatography. Urine concentrations remained above the MIC90 for Escherichia coli (4.0 micrograms/mL) and Proteus mirabilis (1.0 micrograms/mL) for over 24 h after doses of 2.2 mg/kg (8.1 micrograms/mL) and 4.4 mg/kg (29.6 micrograms/mL), the interval between treatments for ceftiofur sodium in dogs, whereas urine concentrations 24 h after dosing at 0.22 mg/kg (0.1 mg/Ib) were below the MIC90 for E. coli and P. mirabilis (0.6 microgram/mL). Plasma concentrations were dose-proportional, with peak concentrations of 1.66 +/- 0.0990 micrograms/mL, 8.91 +/- 6.42 micrograms/mL, and 26.7 +/- 1.07 micrograms/mL after doses of 0.22, 2.2, and 4.4 mg/kg, respectively. The area under the plasma concentration versus time curve, when normalized to dose, was similar across all dosage groups.
authors.affiliation: Animal Health Drug Metabolism, Upjohn Company, Kalamazoo, MI 49001, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Brown
authors.forename: T S
authors.initials: TS
authors.lastname: Arnold
authors.forename: P J
authors.initials: PJ
authors.lastname: Hamlow
authors.forename: A K
authors.initials: AK
authors.lastname: Speedy
authors.forename: N L
authors.initials: NL
authors.lastname: Deleeuw
authors.forename: V L
authors.initials: VL
authors.lastname: Hubbard
authors.forename: J K
authors.initials: JK
authors.lastname: Callahan
authors.forename: S D
authors.initials: SD
authors.lastname: Folz
authors.forename: R L
authors.initials: RL
authors.lastname: Janose
authors.forename: T F
authors.initials: TF
authors.lastname: Flook
mesh_terms: D000818:Animals; D002511:Cephalosporins / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D003198:Computer Simulation; D004285:Dogs / Q000097:blood / Q000378:metabolism* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects; D007279:Injections, Subcutaneous / Q000662:veterinary; D008297:Male; D011513:Proteus mirabilis / Q000187:drug effects; D012044:Regression Analysis
chemical_list: D002511:Cephalosporins; C053503:ceftiofur