Pharmacokinetics and pharmacodynamics of newer macrolides

Requirements for the antimicrobial activity of an antibiotic are: (1) binding of the drug to a specific site in the bacteria; (2) occupation of a critical number of binding sites; and (3) persistence at these binding sites for a sufficient time. With concentration-dependent antibiotics the ratio of the peak serum drug concentration to the MIC of a pathogen is the primary determinant of bacterial killing; with concentration-independent antibiotics it is the length of time serum concentration remains above the MIC, rather than the peak level. The pharmacokinetics of the new macrolides azithromycin and clarithromycin differ notably from those of conventional antibiotics in a more rapid and extensive distribution to body tissues. Because of these unique tissue pharmacokinetics, the pharmacodynamic models that apply to other classes of antibiotics may not explain the antimicrobial activity and clinical efficacy of azithromycin and clarithromycin.