title: Pharmacokinetics and ex-vivo pharmacodynamics of cefquinome against Klebsiella pneumonia in healthy dogs.
abstract: A two-period cross-over study was carried to investigate the pharmacokinetics (PK) and ex-vivo pharmacodynamics (PD) of cefquinome when administrated intravenously (IV) and intramuscularly (IM) in seven healthy dogs at a dose of 2 mg/kg of body weight. Serum concentrations were determined by HPLC-MS/MS assay and cefquinome concentration vs. time data after IV and IM were best fit to a two-compartment open model. Cefquinome mean values of area under concentration-time curve (AUC) were 5.15 μg · h/mL for IV dose and 4.59 μg · h/mL for IM dose. Distribution half-lives and elimination half-lives after IV dose and IM dose were 0.27 and 0.44 h, 1.53 and 1.94 h, respectively. Values of total body clearance (ClB ) and volume of distribution at steady-state (Vss ) were 0.49 L · kg/h and 0.81 L/kg, respectively. After IM dose, Cmax was 2.53 μg/mL and the bioavailability was 89.13%. For PD profile, the determined MIC and MBC values against K. pneumonia were 0.030 and 0.060 μg/mL in MHB and 0.032 and 0.064 μg/mL in serum. The ex vivo time-kill curves also were established in serum. In conjunction with the data on MIC, MBC values and the ex vivo bactericidal activity in serum, the present results allowed prediction that a single cefquinome dosage of 2 mg/kg may be effective in dogs against K. pneumonia infection.
authors.affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
authors.forename: B
authors.initials: B
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Gu
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Gu
authors.forename: N
authors.initials: N
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Shen
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Ding
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D002511:Cephalosporins / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004285:Dogs / Q000097:blood / Q000378:metabolism*; D006207:Half-Life; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C068212:cefquinome