title: Direct lung delivery of para-aminosalicylic acid by aerosol particles.
abstract: Para-aminosalicylic acid (PAS), a tuberculostatic agent, was formulated into large porous particles for direct delivery into the lungs via inhalation. These particles possess optimized physical properties for deposition throughout the respiratory tract, a drug loading of 95% by weight and physical stability over 4 weeks at elevated temperatures. Upon insufflation in rats, PAS concentrations were measured in plasma, lung lining fluid and homogenized whole lung tissue. Systemic drug concentrations peaked at 15 min, with a maximum plasma concentration of 11+/-1 microg/ml. The concentration in the lung lining fluid was 148+/-62 microg/ml at 15 min. Tissue concentrations were 65+/-20 microg/ml at 15 min and 3.2+/-0.2 microg/ml at 3h. PAS was cleared within 3 h from the lung lining fluid and plasma but was still present at therapeutic concentrations in the lung tissue. These results suggest that inhalation delivery of PAS can potentially allow for a reduction in total dose delivered while providing for higher local and similar peak systemic drug concentrations as compared to those obtained upon oral PAS dosing. Similar particles could potentially be used for the delivery of additional anti-tuberculosis agents such as rifampicin, aminoglucosides or fluoroquinolones.
authors: Division of Engineering and Applied Sciences, Department of Physics, Harvard University, 29 Oxford St., Cambridge, MA 02138, USA.
authors: N
authors: N
authors: Tsapis
authors: D
authors: D
authors: Bennett
authors: K
authors: K
authors: O'Driscoll
authors: K
authors: K
authors: Shea
authors: M M
authors: MM
authors: Lipp
authors: K
authors: K
authors: Fu
authors: R W
authors: RW
authors: Clarke
authors: D
authors: D
authors: Deaver
authors: D
authors: D
authors: Yamins
authors: J
authors: J
authors: Wright
authors: C A
authors: CA
authors: Peloquin
authors: D A
authors: DA
authors: Weitz
authors: D A
authors: DA
authors: Edwards
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D010131:Aminosalicylic Acid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001992:Bronchoalveolar Lavage Fluid; D004339:Drug Compounding / Q000379:methods; D008168:Lung / Q000378:metabolism; D008297:Male; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000336:Aerosols; D000995:Antitubercular Agents; D010131:Aminosalicylic Acid