title: Pharmacokinetic evaluation of tobramycin in the alveolar lining fluid of the rat after endotracheal administration.
abstract: Using bronchoalveolar lavage (BAL) we evaluated the concentration-time profile of tobramycin in the alveolar lining fluid (ALF) of rats after direct endotracheal instillation (1.5 mg/kg) and aerosolization (10 mg/ml for 15 min). Very high and long-persisting concentrations of tobramycin were reached in ALF after both modes of administration. After aerosolization a peak concentration in ALF of 339 +/- 41 micrograms/ml was reached with a slow but progressive decline to 45 +/- 8 micrograms/ml at 6 h. After direct endotracheal instillation significantly higher (p less than 0.01) concentrations in ALF (peak concentration, 2,100 +/- 16 micrograms/ml) were reached and formed a stable plateau until 4 h after administration, progressively declining thereafter (400 +/- 30 micrograms/ml at 6 h). Systemic vascular absorption from the alveoli was minimal, but it was higher after direct endotracheal instillation (peak serum concentration, 1.55 +/- 0.21 micrograms/ml). We conclude that in view of the favorable pharmacokinetic profile and the minimal systemic absorption, endobronchial administration of aminoglycosides may be a valuable alternative to systemic administration, which eventually can reduce systemic toxicity and the need for therapeutic drug monitoring.
authors.affiliation: Department of Respiratory Diseases, University Hospital, Ghent, Belgium.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Valcke
authors.forename: R A
authors.initials: RA
authors.lastname: Pauwels
mesh_terms: D000287:Administration, Topical; D000336:Aerosols; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000378:metabolism*; D006207:Half-Life; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014031:Tobramycin / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D014132:Trachea
chemical_list: D000336:Aerosols; D014031:Tobramycin