title: Pharmacokinetic and pharmacodynamic testing of marbofloxacin administered as a single injection for the treatment of bovine respiratory disease.
abstract: New approaches in Pharmacokinetic/Pharmacodynamic (PK/PD) integration suggested that marbofloxacin, a fluoroquinolone already licensed for the treatment of bovine respiratory disease at a daily dosage of 2 mg/kg for 3-5 days, would be equally clinically effective at 10 mg/kg once (Forcyl(®)), whilst also reducing the risk of resistance. This marbofloxacin dosage regimen was studied using mutant prevention concentration (MPC), PK simulation, PK/PD integration and an in vitro dynamic system. This system simulated the concentration-time profile of marbofloxacin in bovine plasma established in vivo after a single 10 mg/kg intramuscular dose and killing curves of field isolated Pasteurellaceae strains of high (minimum inhibitory concentration (MIC) MIC ≤ 0.03 μg/mL), average (MIC of 0.12-0.25 μg/mL) and low (MIC of 1 μg/mL) susceptibility to marbofloxacin. The marbofloxacin MPC values were 2- to 4-fold the MIC values for all Mannheimia haemolytica, Pasteurella multocida tested. Marbofloxacin demonstrated a concentration-dependent killing profile with bactericidal activity observed within 1 h for most strains. No resistance development (MIC ≥ 4 μg/mL) was detected in the dynamic tests. Target values for risk of resistance PK/PD surrogates (area under the curve (AUC) AUC(24 h) /MPC and T(>MPC) /T(MSW) ratio) were achieved for all clinically susceptible pathogens. The new proposed dosing regimen was validated in vitro and by PK/PD integration confirming the single-injection short-acting antibiotic concept.
authors: Le Petit Curtil, Sainte Bénigne, France.
authors: M
authors: M
authors: Vallé
authors: M
authors: M
authors: Schneider
authors: D
authors: D
authors: Galland
authors: H
authors: H
authors: Giboin
authors: F
authors: F
authors: Woehrlé
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D002417:Cattle / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006207:Half-Life; D008297:Male; D016978:Mannheimia haemolytica / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D015661:Pasteurellaceae / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C080260:marbofloxacin