Metabolism and the fluoroquinolones

Quinolones differ considerably with respect to the relative importance of nonrenal drug elimination mechanisms. The extent to which the fluoroquinolones undergo biotransformation in the liver ranges from approximately 50 percent for pefloxacin to about 6 percent for ofloxacin. Although glucuronide conjugates have been identified as minor metabolites for some agents, most metabolic reactions involving quinolones occur through microsomal oxidative mechanisms at the cytochrome P-450 site. These metabolic alterations involve the piperazinyl moiety and usually result in compounds with significantly less microbiologic activity than the parent drugs. Of particular importance is the varying extent of formation of the oxoquinolone metabolite with all fluoroquinolones except ofloxacin. Available evidence suggests that the inhibition of metabolism of drugs such as theophylline and caffeine by quinolones is related to the production of the oxoquinolone metabolite. With all antibiotics, differences in microbiologic activity and pharmacokinetics influence the choice of one agent over another for individual patient selection or consideration for hospital formulary inclusion. For the quinolones the degree and type of metabolism may be a strong factor in this selection process.