Ritrovato C A, Deeter R G
Drug Regulatory Affairs, Hoffmann-La Roche, Inc., Nutley, NJ 07110.
Pharmacotherapy. 1991;11(1):38-49.
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.
抗菌药物在肺部的渗透被认为可预测其在下呼吸道感染治疗中的疗效。肺部渗透研究通常针对新型抗菌药物开展,以阐明其在治疗此类感染中的潜在效用。尽管可能会得出一些非常有用的信息,但这些研究因技术难题、理论假设和诸多复杂因素而变得复杂。已发表了许多描述喹诺酮类药物渗透至唾液、痰液、支气管分泌物和肺组织的研究。一般而言,肺组织中的喹诺酮浓度是血清水平的1.5至4倍,而痰液和支气管分泌物中的浓度等于或低于血清浓度,在唾液中的渗透则更低。根据喹诺酮类药物在唾液、痰液和支气管分泌物中的渗透情况以及其对链球菌的体外边际活性预测的失败率,与临床疗效数据并不始终相关。鉴于此类相互矛盾的数据以及喹诺酮类药物在肺组织中的高渗透性,唾液、痰液和支气管分泌物研究的相关性应重新评估。新型喹诺酮类药物在下呼吸道感染治疗中的效用只能通过精心设计的临床试验来确定。