Pulmonary Disposition of Tobramycin^1,2

Abstract

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.

Lung microdialysis—A powerful tool for the determination of exogenous and endogenous compounds in the lower respiratory tract (mini-review)

“…However, signifi cant differences of antibiotic concentrations have been described between bronchial secretions and acini in the lower respiratory tract. 48 • Correlating pharmacokinetic data to a histological site. For biopsy with consecutively tissue homogenization admixture of concentrations of blood, and intracellular and extracellular contents is unavoidable.…”

Phase I, Single-Dose, Dose-Escalating Study of Inhaled Dry Powder Capreomycin: a New Approach to Therapy of Drug-Resistant Tuberculosis

“…The parenteral administration of aminoglycosides in humans, however, is associated with relatively low lung concentrations of these antibiotics, and high peak serum concentrations (C max ) are needed to obtain microbiologically active concentrations in the alveoli, in the pulmonary interstitium, and intracellularly within macrophages, the most common sites of M. tuberculosis infection. In the few published clinical studies specifically evaluating alveolar lining fluid concentrations of aminoglycosides after systemic administration, alveolar concentrations ranged from 32% to 50% of the peak systemic concentration (9)(10)(11). Furthermore, preclinical studies of capreomycin pharmacokinetics in mice have shown that parenteral doses penetrate poorly into the lung (12).…”

Penetration of cefpodoxime proxetil in lung parenchyma and epithelial lining fluid of noninfected patients

“…Concentrations in ELF were well correlated with concentrations in plasma, with mean ratios of 10.8 and 6.05% in groups A and B, respectively. Previous studies have evaluated the penetration of antibiotics into the ELF with very different results: the ratios of concentrations in ELF to concentrations in serum were 17% for roxithromycin (3), 53% for ampicillin, 51% for sulbactam (16), and 50% for tobramycin (2). These variations could have resulted from two main differences in these studies.…”

“…(i) The modes of administration were different, since tobramycin and ampicillin-sulbactam were administered intravenously (over 30 min for the P-lactams), whereas cefpodoxime and roxithromycin were administered orally. (ii) The sampling times could be considered the times of maximum concentrations in plasma for all of the drugs except tobramycin, for which the sampling times ranged from 1 to 10 h (similarly, the doses ranged (2,8). We notice, however, that all the pathologies, even the variable ones, might be responsible for an increase in alveolar capillary permeability due to edema or interstitial inflammation.…”