Inhalational Therapy for Pulmonary Arterial Hypertension: Current Status and Future Prospects

This review summarizes the pathophysiology and current therapeutic and drug delivery strategies for pulmonary arterial hypertension (PAR), a rare but devastating disorder of the pulmonary circulation affecting 50,000 to 100,000 persons in the United States. Chief clinical features of PAH include increased mean pulmonary arterial pressure (>25 mm Hg) and right ventricular and smooth muscle hypertrophy. A wide variety of agents have been studied fur use as anti-PAR drugs, including prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors, to name a few. However, a major shortcoming of anti-PAR medications is their short half-lives, requiring them to be administered via parenteral routes, which lead to undesirable side effects, including systemic vasodilation. Inhalational delivery of anti-PAR drugs provides an attractive alternative to conventional routes, with ease of administration and minimal systemic vasodilation. Recently, the U.S. Food and Drug Administration approved inhalable iloprost (Ventavis (R)), a prostacyclin analogue, for PAR treatment. Other drugs being studied for their potential in inhalable PAR therapy include PGE1, treprostinil, vasoactive intestinal peptide, and fasudil. Controlled-release inhalable delivery systems for anti-PAR medications have also been proposed to facilitate long-term and selective vasodilation of pulmonary arteries. Extensive studies are warranted to develop safe and effective drug delivery systems that will provide a better quality of life to patients.