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Respiratory tract penetration of quinolone antimicrobials: a case in study
1Drug Regulatory Affairs, Hoffmann-La Roche, Inc., Nutley, NJ 07110.
Abstract:
Antimicrobial lung penetration is thought to be predictive of efficacy in the treatment of lower respiratory tract infections. Lung penetration studies are commonly conducted with new antimicrobial agents to elucidate their potential utility in treating such infections. Although some very useful information may emerge, these studies are complicated by technical difficulties, theoretical assumptions, and numerous intricacies. Many studies describing quinolone penetration into saliva, sputum, bronchial secretions, and lung tissue have been published. In general, quinolone concentrations in lung tissue are 1.5-4 times the serum levels, whereas those in sputum and bronchial secretion are equal to or less than serum, and penetration into saliva is even less. The failure rate predicted from saliva, sputum, and bronchial secretion penetration and marginal in vitro activity of quinolones against streptococci does not consistently correlate with clinical efficacy data. In light of such conflicting data and the high lung tissue penetration of quinolones, the relevance of saliva, sputum, and bronchial secretion studies should be reevaluated. The utility of investigational quinolones in the treatment of lower respiratory tract infections can be determined only by well-designed clinical trials.
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