Formulation of aerosolized therapeutics.
Pseudomonas aeruginosa (PA), which colonizes the airways of approximately 90% of patients with cystic fibrosis (CF) at some point during their lives, is an important contributor to the vicious cycle of infection and inflammation leading to bronchiectasis and eventual respiratory failure. Oral antibiotic therapy is often ineffective in treating PA infections. Instead, in-hospital IV aminoglycoside therapy administered in combination with other IV antibiotics, such as beta-lactams or quinolones, is the mainstay of treatment. The specific chemical and physical properties of CF sputum require high serum antibiotic levels for effective antimicrobial treatment; however, IV aminoglycoside therapy is associated with an increased risk of ototoxicity and nephrotoxicity. In an attempt to avoid systemic toxicity and effectively treat PA infections, clinicians have combined IV antibiotics with sterile solutions of saline or water to aerosolize the mixture for inhalation. Experience with such "home brews" has clearly demonstrated that IV preparations are neither intended nor medically indicated for inhalation. Patients may experience coughing, mucosal irritation, or bronchospasm in response to the preservatives, stabilizing agents, and other additives commonly found in IV preparations. While the rationale for aerosolized drug delivery remains compelling, concerns about uniform dose delivery, ineffective nebulization, and therapeutic adherence arise. Since the 1940s, when these efforts began, ongoing research and clinical trials have identified several additional factors affecting inhaled drug delivery and deposition in the airways. This article chronicles some of the challenges faced by researchers and elucidates factors critical to the reformulation of a safe and effective antibiotic solution for aerosolized delivery.
Kuhn
R J
RJ
Division of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0293, USA. rjkuhn1@pop.uky.edu
D000336:Aerosols; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001987:Bronchiectasis / Q000097:blood / Q000188:drug therapy; D003550:Cystic Fibrosis / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D009330:Nebulizers and Vaporizers; D009894:Opportunistic Infections / Q000097:blood / Q000188:drug therapy*; D011552:Pseudomonas Infections / Q000097:blood / Q000188:drug therapy*
D000336:Aerosols; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents