A Pharmacokinetic and Bioavailability Study of Mannitol for Inhalation Using Normal Subjects

The study has an open-label, randomized, crossover design, in which each subject will receive mannitol powder for inhalation using a dry powder inhaler with and without premedication with a bronchodilator, mannitol powder for inhalation in capsules administered orally, and mannitol in a commercial formulation designed for intravenous use.

Inclusion Criteria:

• Subject has signed a written informed consent form.
• Subject is a normal male volunteer between 18 and 65 years of age.
• Subject is willing to comply with the procedures of the study and to remain in the clinical unit for the scheduled visits.
• Subject is willing to abstain from chewing gum for the duration of the study.

Exclusion Criteria:

• Subject has asthma or other disease affecting the lungs or airways.
• Subject has a history indicating possible airway hyperresponsiveness.
• Subject is allergic to mannitol or gelatin or a known intolerance to intravenous mannitol.
• Subject uses inhaled drugs (legal or illegal).
• Subject uses oral bronchodilator drugs.
• Subject has celiac disease, Crohn's disease or other disease affecting intestinal absorption.
• Subject has renal impairment or other condition that would affect urine collection.
• Subject's weight deviates by more than 15% from the ideal weight listed for his height in the Metropolitan Life table.
• Subject is a smoker.
• Subject has participated in another clinical trial within the past 30 days.
• Subject has used chewing gum within the past 72 hours.
• Subject needs to use bisphosphonates, non-steroidal anti-inflammatory agents, or other drugs known to affect intestinal permeability on a chronic basis.
• Subject has used non-steroidal anti-inflammatory agents within the past 72 hours