Poeppl Wolfgang, Lingscheid Tilman, Bernitzky Dominik, Donath Oliver, Reznicek Gottfried, Zeitlinger Markus, Burgmann Heinz
Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University Vienna, Vienna, Austria.
Pharmacology. 2014;93(1-2):65-8. doi: 10.1159/000357569. Epub 2014 Feb 5.
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.
近年来，磷霉素一直是众多体内药效学模型研究的对象。本研究旨在测定实验室大鼠体内磷霉素的药代动力学，以便为未来的啮齿动物模型制定合适的给药方案。将磷霉素以75、200和500mg/kg体重的单剂量腹腔注射给每个剂量组的4只斯普拉格-道利大鼠。在8小时内采集血样，并通过高效液相色谱-质谱法测定磷霉素浓度。磷霉素呈现出剂量成正比的药代动力学特征，最大浓度与浓度-时间曲线下面积（AUC）的相关性为0.99。腹腔注射75、200或500mg/kg体重磷霉素后，平均AUC0-8分别为109.4、387.0和829.1µg·h/ml。总之，每天3次、200-500mg/kg的给药方案适合在实验室大鼠中获得血清浓度，随着时间的推移能密切模拟人体血清浓度。
