Species-related stereoselective disposition of ofloxacin in the rat, dog and monkey

Xenobiotica. 1992 Apr;22(4):439-50. doi: 10.3109/00498259209046656.

Abstract

1. The stereoselective disposition of ofloxacin (OFLX) was studied in rats, dogs and monkeys after oral administration of racemic OFLX. 2. In rats serum concentrations of (R)-(+)-OFLX were much greater than those of (S)-(-)-OFLX, which is the active form of OFLX. In monkeys, by contrast, serum concentrations of (S)-(-)-OFLX predominated over (R)-(+)-OFLX levels. In dogs there were no differences in AUC or Cmax between the enantiomers. Thus, there exists a species-related difference in the stereoselective disposition of OFLX. 3. In rats the stereoselective differences were mainly due to stereoselective glucuronidation; OFLX is hardly metabolized in dogs, monkeys and humans. 4. In monkeys the AUC of (S)-(-)-OFLX was increased by co-administration of the (R)-(+)-form, indicating that the stereoselectivity of OFLX disposition in monkeys may be caused by competition between the enantiomers for renal excretion, especially for renal tubular secretion.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Infective Agents*
  • Dogs
  • Female
  • Fluoroquinolones*
  • Inactivation, Metabolic
  • Injections, Intravenous
  • Kidney / metabolism
  • Macaca fascicularis
  • Male
  • Metabolic Clearance Rate
  • Ofloxacin / analogs & derivatives
  • Ofloxacin / metabolism
  • Ofloxacin / pharmacokinetics*
  • Rats
  • Species Specificity
  • Stereoisomerism
  • Substrate Specificity

Substances

  • Anti-Infective Agents
  • Fluoroquinolones
  • desmethylofloxacin
  • ofloxacin O-glucuronide
  • ofloxacin N-oxide
  • Ofloxacin