Pharmacokinetics of arbekacin in bronchial epithelial lining fluid of healthy volunteers.

Abstract

Arbekacin is a unique aminoglycoside antibiotic with anti-methicillin-resistant Staphylococcus aureus activity. The efficacy of aminoglycosides is related to their serum maximum concentration. Local concentration of antibiotics in pulmonary epithelial lining fluid, rather than its serum concentration, can help determine its clinical efficacy more precisely for treatment of respiratory infectious disease. The objective of this study was to sequentially measure arbekacin concentration in epithelial lining fluid after infusion of a single clinically available dose. After the initial blood sampling, arbekacin was intravenously infused into 6 healthy volunteers over 1h. Epithelial lining fluid and serum samples were collected by bronchoscopic microsampling 1, 1.5, 2, 2.5, 3, 4, 5, and 6h after the start of 200mg arbekacin infusion. Each probe sampled 10.1±5.2μl bronchial epithelial lining fluid. The sample dilution factor was 266.7±157.1. Drug concentration was successfully measured in all but 2 of the epithelial lining fluid samples. The maximum concentration of arbekacin in epithelial lining fluid and serum was 10.4±1.9μg/ml and 26.0±12.2μg/ml, respectively. The ratio of the maximum drug concentration in the epithelial lining fluid to that in the serum was 0.47±0.19. The maximum concentration of epithelial lining fluid reached levels that would effectively treat most clinical strains of methicillin-resistant S. aureus.