title: Comparative study of the disposition of levofloxacin, netilmicin and cefepime in the isolated rat lung.
abstract: An experimental model of artificially perfused and mechanically ventilated lung has been applied to compare the kinetic behaviour of levofloxacin, cefepime and netilmicin in this body tissue. The study has been performed to explore the usefulness of the isolated lung technique in the pharmacokinetic field, particularly to study the disposition of antibiotics in pulmonary tissue. The lung was perfused with Krebs-Henseleit medium containing 3% bovine albumin at a flow rate of 5 mL min(-1). It was ventilated at 60 respirations/min with a 2-mL tidal volume of air previously humidified and warmed to 37 degrees C. The concentrations of the above antibiotics were determined by HPLC techniques and the outflow curves were analysed by stochastic, as well as by model-dependent, methods. The results show pharmacokinetic differences among these antibiotics, which are in accordance with previously reported data, levofloxacin being the drug with the highest distribution coefficient in this tissue (1.25 +/- 0.14 vs 0.39 +/- 0.07 and 0.41 +/- 0.06 mL g(-1) for netilmicin and cefepime, respectively). Accordingly, the isolated lung of the rat, under the experimental conditions used here, constitutes an alternative model to be incorporated to pharmacokinetic studies with a great potential use for those drugs that show a pharmacological or toxicological action depending on the kinetic profile in the lung tissue.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Salamanca, Avda Campo Charro s/n, 37007, Salamanca, Spain.
authors.forename: María Santos
authors.initials: MS
authors.lastname: Martínez Martínez
authors.forename: Clara Isabel Colino
authors.initials: CI
authors.lastname: Gandarillas
authors.forename: José
authors.initials: J
authors.lastname: Martínez Lanao
authors.forename: Amparo
authors.initials: A
authors.lastname: Sánchez Navarro
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D000077723:Cefepime; D002511:Cephalosporins / Q000493:pharmacokinetics*; D007700:Kinetics; D064704:Levofloxacin; D008168:Lung; D008297:Male; D009428:Netilmicin / Q000493:pharmacokinetics*; D015242:Ofloxacin / Q000493:pharmacokinetics*; D009924:Organ Culture Techniques / Q000662:veterinary; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial / Q000662:veterinary; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D009428:Netilmicin; D064704:Levofloxacin; D000077723:Cefepime; D015242:Ofloxacin