Nebulized therapies for childhood pulmonary hypertension: An in vitro model

• Published in: Pediatric pulmonology Vol. 41; no. 7; pp. 666 - 673
• Main Authors: Katz, Sherri L., Adatia, Ian, Louca, Emily, Leung, Kitty, Humpl, T., Reyes, Janette T., Coates, Allan L.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2006; Wiley-Liss
• Subjects: Adolescent; aerosol; Antihypertensive Agents - administration & dosage; Biological and medical sciences; Child; endothelin receptor antagonist; Epoprostenol - administration & dosage; estimated pulmonary deposition; Humans; Hypertension, Pulmonary - drug therapy; Medical sciences; Models, Theoretical; nebulizers; Nebulizers and Vaporizers; Piperazines - administration & dosage; Pneumology; prostacyclin; pulmonary hypertension; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; pulmonary vasodilators; Purines; Pyridines - administration & dosage; sildenafil; Sildenafil Citrate; Sulfones; Tetrazoles - administration & dosage; therapy; Vasodilator Agents - administration & dosage; pulmonary vasodilators; Pediatrics; Endothelin; Prostaglandin I2; Lung; Cardiovascular disease; Antagonist; Child; estimated pulmonary deposition; Deposition; Biological receptor; aerosol; Human; Respiratory disease; prostacyclin; therapy; In vitro; sildenafil; Pulmonary hypertension; Treatment; nebulizers; Aerosols; endothelin receptor antagonist; Models; Nebulizer
• ISSN: 8755-6863; 1099-0496
• DOI: 10.1002/ppul.20431

Objectives Sildenafil, tezosentan, and prostacyclin reduce pulmonary vascular pressures in pulmonary hypertension, but have potential to vasodilate the systemic circulation. Nebulized vasodilators allow targeted drug delivery, high local drug concentrations, less systemic hypotension, and better matching of the lung's ventilation and perfusion. We aimed to estimate pulmonary deposition of these drugs from commonly employed nebulizers using in vitro techniques and to create a mathematical model to predict inspired mass of aerosol. Design Lung deposition was estimated by characterization of drug output and particle size distribution (PSD) of nebulizers using helium‐neon laser diffraction techniques. A mathematical model for each device was created to estimate pulmonary deposition using patients' breathing patterns and was verified with a mechanical‐breathing model. Results Total output and PSD were similar for the Hudson Updraft II and Whisperjet nebulizers, consisting of half the nebulizer's charge, with ¼ of particles ≤5 µm, in the respirable fraction (RF). Drug output increased with inspiratory flow for the Pari LC Star. Differences were noted in device performance, depending on the drug tested. Estimated pulmonary deposition (mean, 95% CI) was 8.1 (7.2, 9.0)% of the initial drug charge for the Hudson Updraft II, 6.4 (5.8, 7.0)% for the Whisperjet, and 33.0 (28.3, 37.9)% for the Pari LC Star. A mechanical model was consistent with our mathematical model. Conclusions All drugs could be nebulized, but expected pulmonary deposition varied depending on the nebulizer and drug. Pediatr Pulmonol. 2006; 41: 666–673. © 2006 Wiley‐Liss, Inc.