Pharmacokinetics of quinolones: Newer aspects

Abstract

Differences in pharmacokinetic properties are emerging as important determinants in distinguishing among clinical uses of individual new quinolone antimicrobial agents. Selected data on pharmacokinetics, new pharmacokinetic studies, and pharmacodynamics are reviewed, with reference to norfloxacin, ciprofloxacin, ofloxacin, pefloxacin, enoxacin, fleroxacin, lomefloxacin, and other new quinolones. Considering pharmacokinetics, oral bioavailability is excellent (greater than 95%) for most quinolones. Differences in peak serum concentrations and beta-half-lives of elimination exist, however, and are reflected in up to ten-fold differences in values of the area under the curve of serum concentration versus time for administration of similar drug doses. As suggested by high apparent volumes of distribution and low binding to serum proteins, penetration into many body tissues and fluids is favorable. Considering new findings, orally administered ciprofloxacin has been found to be absorbed primarily in the duodenum and jejunum. Studies also suggest this drug to be cleared by transepithelial elimination into the bowel lumen as well as by the renal route. Oral bioavailability of quinolones has been demonstrated to be in general good in ill as well as healthy subjects but is reduced on co-administration with magnesium- and aluminum-containing acids, sucralfate (which contains aluminum), or ferrous sulfate. Pharmacodynamic parameters, such as the relationship of serum concentrations and drug potency in vitro to clinical response and suppression of bacterial resistance, have been little studied and merit further investigation.