title: Species-related stereoselective disposition of ofloxacin in the rat, dog and monkey.
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.
authors.affiliation: Drug Metabolism and Analytical Chemistry Research Center, Developmental Research Laboratories, Daiichi Pharmaceutical Co. Ltd., Tokyo, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Okazaki
authors.forename: T
authors.initials: T
authors.lastname: Kurata
authors.forename: H
authors.initials: H
authors.lastname: Hakusui
authors.forename: H
authors.initials: H
authors.lastname: Tachizawa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents; D004285:Dogs; D005260:Female; D024841:Fluoroquinolones; D008658:Inactivation, Metabolic; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D008657:Metabolic Clearance Rate; D015242:Ofloxacin / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D013045:Species Specificity; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; C054988:desmethylofloxacin; C076660:ofloxacin O-glucuronide; C054987:ofloxacin N-oxide; D015242:Ofloxacin