title: Assessing pharmacokinetics of different doses of fosfomycin in laboratory rats enables adequate exposure for pharmacodynamic models.
abstract: Fosfomycin has been the subject of numerous pharmacodynamic in vivo models in recent years. The present study set out to determine fosfomycin pharmacokinetics in laboratory rats to enable adequate dosing regimens in future rodent models. Fosfomycin was given intraperitoneally as single doses of 75, 200 and 500 mg/kg bodyweight to 4 Sprague-Dawley rats per dose group. Blood samples were collected over 8 h and fosfomycin concentrations were determined by HPLC-mass spectrometry. Fosfomycin showed a dose-proportional pharmacokinetic profile indicated by a correlation of 0.99 for maximum concentration and area under the concentration-time curve (AUC). The mean AUC0-8 after intraperitoneal administration of 75, 200 or 500 mg/kg bodyweight fosfomycin were 109.4, 387.0 and 829.1 µg·h/ml, respectively. In conclusion, a dosing regimen of 200-500 mg/kg 3 times daily is appropriate to obtain serum concentrations in laboratory rats, closely mimicking human serum concentrations over time.
authors: Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University Vienna, Vienna, Austria.
authors: Wolfgang
authors: W
authors: Poeppl
authors: Tilman
authors: T
authors: Lingscheid
authors: Dominik
authors: D
authors: Bernitzky
authors: Oliver
authors: O
authors: Donath
authors: Gottfried
authors: G
authors: Reznicek
authors: Markus
authors: M
authors: Zeitlinger
authors: Heinz
authors: H
authors: Burgmann
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005578:Fosfomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin