Wednesday, October 21, 2015 8:24:41 PM
PUR1900 is formulated with Pulmatrix's proprietary iSPERSE™ (Inhaled Small Particles Easily Respirable and Emitted) dry powder delivery platform, which seeks to improve therapeutic delivery to the lungs by maximizing local concentrations and reducing systemic side effects.
Researchers compared the pharmacokinetics and potency of itraconazole against two other antifungal compounds -- amphotericin B and voriconazole -- following intratracheal instillation in rats at doses of up to 1.5 mg/kg. Lung and plasma samples were collected beginning five minutes after instillation for seven to fourteen days. In vitro susceptibility testing was performed using broth microdilution testing against A. fumigatus, as well as A. niger, A. flavus, and 10 to 20 strains of Candida spp.
In rat pharmacokinetic studies, itraconazole showed a long duration of lung retention, with some clearance over a one week period. Subsequent studies with PUR1900 dry powder demonstrated that PUR1900 maintains high concentrations of itraconazole in both lung tissue and in bronchoalevolar lavage samples. Amphotericin B lung concentrations remained constant over one week, while voriconazole was rapidly absorbed and cleared from the lungs. Most notably, the percentage of administered drug recovered in lung tissue for itraconazole was significantly higher than for amphotericin or voriconazole, and itraconazole had a long lung half-life, which may lead to less frequent dosing in the clinic. All three compounds exhibited potent activity against A.fumigatus in vitro.
"The pharmacokinetics and potency of PUR1900 demonstrate that the drug is likely to achieve the high local concentrations needed to combat fungal infections caused by Aspergillus spp while overcoming oral bioavailability limitations and minimizing systemic side effects such as drug interactions," said David L. Hava, PhD, Pulmatrix's chief scientific officer.
Dr. Richard Moss, emeritus professor of pediatrics at Stanford University, said: "Use of new technologies such as iSPERSE™ to deliver high concentrations of inhaled antifungal drugs directly to the lung have the potential to effectively prevent or treat serious fungal infections or allergies while avoiding problems of toxicities or resistance encountered with systemic use of oral or parenteral antifungals."
Link to Abstract: http://onlinelibrary.wiley.com/doi/10.1002/ppul.23297/full - Poster #393
The 29th Annual North American Cystic Fibrosis Conference is a scientific meeting for medical professionals in the field of cystic fibrosis research and care. The conference is sponsored by The Cystic Fibrosis Foundation.
About Pulmatrix
Pulmatrix is a clinical stage biopharmaceutical company developing innovative inhaled therapies to address serious pulmonary disease using its patented iSPERSE™ technology. The Company's proprietary product pipeline is focused on advancing treatments for rare diseases, including PUR1900, an inhaled anti-fungal for patients with cystic fibrosis (CF), as well as PUR1500, an inhaled product for the treatment of idiopathic pulmonary fibrosis. In addition, Pulmatrix is pursuing opportunities in major pulmonary diseases through collaborations, including PUR0200, a branded generic in clinical development for chronic obstructive pulmonary disease (COPD). Pulmatrix's product candidates are based on iSPERSE™, its proprietary dry powder delivery platform, which seeks to improve therapeutic delivery to the lungs by maximizing local concentrations and reducing systemic side effects to improve patient outcomes.
For more information, visit www.pulmatrix.com. Follow Pulmatrix on Twitter at https://twitter.com/pulmatrix_inc, and on StockTwits at http://stocktwits.com/pulmatrix.
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