Intrapulmonary Pharmacokinetics of Antibacterial Agents
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Am J Respir Med 2002; 1 (3): 201-209 1175-6365/02/0003-0201/$25.00/0 © Adis International Limited. All rights reserved.
Intrapulmonary Pharmacokinetics of Antibacterial Agents Implications for Therapeutics Loretta M. Chiu and Guy W. Amsden The Clinical Pharmacology Research Center and Department of Adult and Pediatric Medicine, Bassett Healthcare, Cooperstown, New York, USA
Contents Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Factors Influencing Lung Penetration of Antibacterials 2. Data Interpretation . . . . . . . . . . . . . . . . . . . . . 3. Penetration Properties of Key Antibacterial Classes . . 3.1 β-Lactam Agents . . . . . . . . . . . . . . . . . . . 3.2 Aminoglycosides . . . . . . . . . . . . . . . . . . . . 3.3 Glycopeptides . . . . . . . . . . . . . . . . . . . . . 3.4 Macrolides . . . . . . . . . . . . . . . . . . . . . . . 3.5 Fluoroquinolones . . . . . . . . . . . . . . . . . . . . 4. Relationship of Drug Penetration to Clinical Efficacy . . 5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . .
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The idea of studying the pharmacokinetics and pharmacodynamics of antibacterials in order to predict their efficacy has long been of interest. Traditionally, serum drug concentrations have been evaluated against the minimum inhibitory concentration (MIC) of a given pathogen; however, infection site-specific data continue to gain interest from clinicians. Despite methodological limitations, progress in techniques has improved the clinical significance of data generated. Rather than using tissue homogenates which fail to differentiate between interstitial and intracellular concentrations, newer collection techniques focus on sampling of matrices that allow for this differentiation. These collection techniques now allow one to accurately describe β-lactam and aminoglycoside interstitial penetrations, as well as, the interstitial and phagocytic concentrations of macrolides and fluoroquinolones. By using these specific data and the MICs of infecting pathogens, it is hoped that con
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