Tobramycin penetration into epithelial lining fluid of patients with pneumonia.
OBJECTIVE
To study the penetration of tobramycin in lung tissue evaluated as the concentration in epithelial lining fluid and to characterize the time course of the drug in the treatment of patients with pneumonia.


METHODS
The subjects were 16 patients with pneumonia and taking tobramycin who had clinical indications for bronchoscopy. Bronchoscopy with bronchoalveolar lavage of the pneumonic area was performed once on each patient 1/2%, 2, 4, or 8 hours after the previous tobramycin dose. Urea was used as an endogenous marker for quantification of epithelial lining fluid obtained at bronchoalveolar lavage. Tobramycin concentrations in serum were measured for all patients at the aforementioned 4 time points. Tobramycin concentration was determined by means of fluorescent polarization immunoassay modified for bronchoalveolar samples.


RESULTS
Levels of tobramycin in the fluid of the epithelial lining were 2.33+/-0.5 at 1/2 hour, 1.67+/-0.6 at 2 hours, 1.62+/-1.19 at 4 hours, and 0.77+/-0.38 microg/mL at 8 hours. The ratio of epithelial lining fluid to serum concentration of tobramycin was 0.30+/-0.03 at 1/2 hour, 0.42+/-0.16 at 2 hours, 0.64+/-0.37 at 4 hours, and 1.53+/-0.76 at 8 hours. The ratio at peak serum time was similar to that reported for tobramycin and netilmicin.


CONCLUSIONS
High peak serum concentrations of tobramycin are necessary to obtain microbiologically active concentrations at the alveolar level. The fluid of the epithelial lining constitutes a deep compartment for aminoglycosides. The disappearance of tobramycin was slower than at the serum level.
Carcas
A J
AJ
Hospital Universitario La Paz and Departamento de Farmacología and Terapéutica, the Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
García-Satué
J L
JL
Zapater
P
P
Frías-Iniesta
J
J
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000188:drug therapy* / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D014018:Tissue Distribution; D014031:Tobramycin / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D014031:Tobramycin