Tissue penetration and pulmonary disposition of tobramycin

Abstract

The pharmacokinetics of tobramycin, including the penetration into suction blister fluid (SBF), has been investigated in 12 patients with a mean age of 69.8 +/- 4.6 yrs, after a single i.m. administration of either 150 or 300 mg. Tobramycin demonstrated a concentration-independent pharmacokinetics and a high diffusion into the extravascular compartment with a penetration index (obtained by the SBF and serum AUC ratio) of 135% with no significant differences between the two groups of patients. Tobramycin was also administered as a single or multiple i.m. dose of 300 mg in 10 intensive care patients undergoing fiberoptic bronchoscopy for diagnostic purposes. The aminoglycoside mean concentration 6h after the single or last administration ranged from 5.3 to 5.5 mg/l and from 3.0 to 3.3 mg/l in alveolar lining fluid (ALF) and macrophages (AM), respectively, thus demonstrating that the once-daily dosage schedule leads to high and persistent levels in the bronchial alveolar tree, exceeding the minimum inhibitory concentrations in vitro for susceptible respiratory pathogens.