Pulmonary disposition of tobramycin.
Each antibiotic has a characteristic penetration into respiratory secretions, influenced by serum concentration, protein binding, transport systems, and the presence of infection. Whereas previous studies have used only bronchial secretions and blood, in the present study, blood, bronchial secretions, and bronchoalveolar lavage (BAL) fluid were analyzed for tobramycin levels. In 10 studies in 9 patients, serum levels were significantly related to BAL fluid levels (r = 0.8, p less than 0.01) when both were expressed as a function of creatinine (mean BAL level +/- SD = 144 +/- 124 micrograms/mg creatinine; serum level, 293 +/- 216 micrograms/mg creatinine). The level of drug penetration in BAL fluid, expressed by the slope of the relationship between blood and fluid, was 0.5. The penetration of tobramycin into bronchial secretions ranged from 0 to 1.4 micrograms/ml, the ratio of secretions to serum being 0.2 (r = 0.68; p less than 0.05). It is concluded that the disposition of tobramycin in bronchial secretions and BAL fluid differ. Thus, sampling both fluids offers a more suitable method to study antibiotic pharmacokinetics in bronchi and alveoli.
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