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It has been over 30 years since the first clinically important
member of the quinolone class, nalidixic acid, was introduced into
medical practice. The modification produced in the quinolone
nucleus by introducing a fluorine at the 6-position led to the
discovery of the newer fluoroquinolones with enhanced antibacterial
activities as compared to nalidixic acid. By now a great deal of
preclinical and clinical experience has been obtained with these
agents. The intense interest in this class of antibacterial agents
by chemists, micro biologists, toxicologists, pharmacologists,
clinical pharmacologists, and clini cians in various disciplines
encouraged us to summarize the information on the history,
chemistry, mode of action and in vitro properties, kinetics and
efficacy in animals, mechanisms of resistance, toxicity, clinical
pharmacology, clinical experience, and future prospects in one
volume of the Handbook of Experimental Pharmacology. As this series
deals predominantly with "experimental" characteristics of drugs,
our volume is dedicated specifically to quinolones and emphasizes
principally their preclinical and clinical phar macological
characteristics, despite the existence of several summaries on
quinolones. The chemistry of the quinolones is described in detail.
The chapter on the mode of action of quinolones reports the
conclusive evidence that gyrase is the intracellular target of the
quinolones; however, another enzyme, topoisomerase IV, may also be
a target for quinolones, and the exact mechanisms by which
quinolones act bactericidally are far from being understood."
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