Aerosolised levofloxacin in cystic fibrosis

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Introduction: Cystic Fibrosis (CF) is a rare autosomal recessive hereditary disease in the Caucasian population, caused by mutations in an epithelial chloride channel. A hallmark of CF is chronic microbial respiratory infection, which has the greatest role in morbidity and mortality of the patients due to progressive tissue damage. Improved high dose antibiotic treatment strategies for Pseudomonas aeruginosa lung infections have improved patients' prognosis. The fluoroquinolone, levofloxacin, is currently being developed for the management of chronic P. aeruginosa infection in CF patients. Levofloxacin inhalation solution (MP-376), which is generally well tolerated in CF patients, reaches high levels in CF sputum with low systemic exposure. In a Phase II study, MP-376 reduced P. aeruginosa sputum density and increased lung function in a dose-dependent manner; twice-daily administration of 240 mg MP-376 was significantly superior over placebo. Areas covered: In this manuscript, we summarise the epidemiology, genetics and pathogenesis of CF and discuss current and future therapeutic options for CF lung disease, emphasising the pharmacokinetics and pharmacodynamics of fluoroquinolone inhalation therapy for the CF-specific bacterial pathogen P. aeruginosa. Expert opinion: Based on its excellent water solubility, levofloxacin is the most promising agent among the fluoroquinolones currently developed for cystic fibrosis, yet only sparse clinical data are currently available to support this notion.

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