PHARMACOKINETICS OF ORAL LIPOIC ACID IN CYSTIC FIBROSIS PATIENTS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Early death remains a hallmark of cystic fibrosis (CF), primarily as a result of progressive lung disease. CF is characterized by lung damage from airways obstructed with thick viscous mucus and exposed to a chronic neutrophilic inflammation with prominent elevations in cytokines, proteases and oxidants. -Lipoic acid (LA) is a dithiol compound with the potential to be of significant benefit to CF patients. In laboratory studies, LA is able to decrease mucus viscoelasticity, downregulate inflammatory cytokines and NF- B, inhibit proteases such as elastase and matrix metalloproteinase-9 (MMP-9) and cause direct and indirect antioxidant effects. Animal studies indicate that LA given systemically results in a significant elevation of airway LA. We hypothesize that CF patients given an oral dose of LA will also show elevations in airway LA levels. LA delivered in this manner may address a number of the pathologic processes within the CF airway. In anticipation of future efficacy trials, the purpose of the current study is to define the airway and blood pharmacokinetics of oral LA in CF patients.