D. Nix, Jerome J. Schentag
Feb 1, 1988
Citations
5
Influential Citations
61
Citations
Journal
The Journal of Clinical Pharmacology
Abstract
T he search for new antimicrobials with greater potency and expanded spectrum of activity has recently produced the 6-fluoroquinolones. These compounds were synthesized, using nalidixic acid and oxolinic acid as prototypes, but have markedly improved potency over these earlier agents against gram-negative and gram-positive bacteria. The 6fluoroquinolones differ in their pharmacokinetic properties; however, the importance of the pharmacokinetic differences between the 6-fluoroquinoJones needs to be explored. This review compares the pharmacokinetics of the fluoroquinolones and nalidixic acid and examines their pharmacokinetic interactions with other drugs. To compare their pharmacodynamics, the serum peak concentration to MIC ratio for some typical isolates will be calculated for each compound. Table I lists the generic names and investigational identification numbers for the compounds to be discussed; their structures are shown in Figure 1. All of the new fluoroquinolones contain 6-fluoroand 7piperazine substituents, which greatly enhance their antimicrobial potency in comparison with nalidixic acid. The seemingly minor differences between the structures of these fluoroquinolones produce marked differences in antimicrobial spectrum and activity, and in pharmacokinetics. In general, structure modifications have been made primarily on ring positions 1, 2, 5, 6, 7, and 8.1 It is not possible to alter the configuration at positions 3 and 4 without complete loss of activity. Modifications at positions 2, 5, and 7 change the absorption and distribution of these compounds, whereas the enhanced antibacterial activities of these compounds comes from the 6-fluoro substituent, having greater activity than any other halogen or any other substituent.1 Recent