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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Airway deposition and clearance and systemic pharmacokinetics of amiloride following aerosolization with an ultrasonic nebulizer to normal airways.

STUDY OBJECTIVES: Airway epithelial ion transport is an important component of the airway defense mechanism, and new therapies that target ion transport are being developed. Amiloride is an example of such a new drug, exerting a dose-dependent action to inhibit Na+ transport. Amiloride may be useful in cystic fibrosis, blocking the characteristic airway epithelial Na+ hyperabsorption that occurs in the disease. To evaluate airway and systemic delivery of amiloride via an ultrasonic nebulizer (Omron NE-UO7), we measured the airway surface concentrations of amiloride in normal volunteers via a novel approach, together with the systemic pharmacokinetics of amiloride. DESIGN: Direct measurement of airway surface liquid, plasma, and urine amiloride concentrations following ultrasonic nebulization. PARTICIPANTS/INTERVENTIONS: Seven normal subjects were studied in the General Clinical Research Center of the University of North Carolina. Following inhalation with amiloride (1 mg/mL, 4.5 mL) for approximately 12 min, a bronchoscopy was performed. Amiloride deposition and clearance from airway surfaces over 1 h were evaluated by transbronchoscopic sampling using preweighed filter papers. Pulmonary and systemic absorption was assessed by measuring drug concentrations in blood and urine. RESULTS: The mean volume aerosolized was 3.5+/-0.3 mL during 12 min of aerosolization time; the mean initial concentration of amiloride on airway surfaces after nebulization was 1.6 x 10(-4) mol/L, with an elimination half life of approximately 23 min. Peak plasma concentrations of amiloride (30 min, 3.36+/-0.70 ng/mL) suggest early absorption across lung surfaces, rather than via the GI route. Mean urinary excretion of amiloride over 72 h was 0.63+/-0.07 mg, with 87% excreted in the first 24 h. CONCLUSIONS: The ultrasonic nebulizer rapidly delivers amiloride to normal conducting airways as assessed by the transbronchoscopic sampling technique. Early blood concentrations of amiloride probably reflect initial absorption across lung surfaces and are a useful index of the efficiency of the machine.[1]


  1. Airway deposition and clearance and systemic pharmacokinetics of amiloride following aerosolization with an ultrasonic nebulizer to normal airways. Noone, P.G., Regnis, J.A., Liu, X., Brouwer, K.L., Robinson, M., Edwards, L., Knowles, M.R. Chest (1997) [Pubmed]
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