Species-related stereoselective disposition of ofloxacin in the rat, dog and monkey.
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.
Okazaki
O
O
Drug Metabolism and Analytical Chemistry Research Center, Developmental Research Laboratories, Daiichi Pharmaceutical Co. Ltd., Tokyo, Japan.
Kurata
T
T
Hakusui
H
H
Tachizawa
H
H
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
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; C054988:desmethylofloxacin; C076660:ofloxacin O-glucuronide; C054987:ofloxacin N-oxide; D015242:Ofloxacin