title: Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin after intravenous and intramuscular administration in beagle dogs.
abstract: 1.The aim of the present study was to determine the PKs of marbofloxacin in beagle dogs after intravenous (i.v.) and intramuscular (i.m.) administration, the ex vivo and in vitro PK/PD indices of marbofloxacin against clinical isolates of Staphylococcus pseudintermedius, and the ex vivo AUC/MIC ratios associated with different levels of antibacterial activity. 2.After i.v. of marbofloxacin (2 mg/kg), the mean ± SEM values of AUC, t1/2β, Vss, and CL were 8.47 ± 3.51 h µg/mL, 8.08 ± 6.25 h, 2.32 ± 1.00 L/kg and 0.23 ± 0.06 L/kg/h and corresponding values after intramuscular injection were 11.37 ± 3.07 h µg/mL, 7.51 ± 3.70, 1.80 ± 0.90 L/kg and 0.17 ± 0.04 L/kg/h. After i.m. administration, a Cmax of 1.76 ± 0.09 µg/mL was achieved at Tmax of 0.47 ± 0.08 h. The ex-vivo AUC/MIC ratios required to produce bacteriostasis, bactericidal action and elimination of S. pseudintermedius were 65.03, 97.02 and 136.84 h. 3.The in vivo AUC/MIC ratios obtained after i.v. and i.m. administration of 2 mg/kg marbofloxacin (67.76 ± 1.23 and 91.18 ± 2.61) were below the ex vivo AUC/MIC ratios required for bactericidal activity and bacterial elimination (97.02 ± 9.24 2 mg/kg and 136.21 ± 7.58), suggesting that the recommended daily dosage (2 mg/kg) may not suffice to kill and eradicate S. pseudintermedius strains encountered in clinical area.
authors.affiliation: Laboratory of Pharmacokinetics and Pharmacodynamics, Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Kyungpook National University , Daegu , Republic of Korea and.
authors.forename: Sileshi
authors.initials: S
authors.lastname: Yohannes
authors.forename: Elias Gebru
authors.initials: EG
authors.lastname: Awji
authors.forename: Seung-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Seung-Chun
authors.initials: SC
authors.lastname: Park
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D015169:Colony Count, Microbial; D018592:Cross-Over Studies; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D024841:Fluoroquinolones / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D013210:Staphylococcus / Q000187:drug effects; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C080260:marbofloxacin
keywords: Beagle dogs; PK/PD; drug resistance; marbofloxacin; staphylococcus pseudintermedius