Stereoselective metabolic disposition of enantiomers of ofloxacin in rats.

1. Stereoselective metabolic disposition of ofloxacin (OFLX) was studied in rats after oral administration of S-(-)-14C-OFLX and R-(+)-14C-OFLX at a dose of 20 mg/kg. 2. Radioactivity of the S-(-)-isomer was eliminated from blood much faster than that of the R-(+)-isomer. Marked differences in pharmacokinetic parameters exist between the enantiomers; the half life and AUC values of R-(+)-OFLX were greater than those of S-(-)-OFLX. Enantiomeric differences were also seen in the excretion of radioactivity, especially in biliary excretion. 3. 31.3 and 7.4% dose were excreted in the 8 h bile as ester glucuronides after oral administration of S-(-)- and R-(+)-OFLX, respectively. The enantiomeric difference in biliary excretion may be caused by stereoselective glucuronidation of S-(-)-OFLX to the ester glucuronide. 4. The metabolite pattern in serum and urine showed that the ester glucuronide of S-(-)-OFLX was more predominant than that of R-(+)-OFLX. 5. The stereoselective ester glucuronidation of the S-(-)-isomer in rats may induce significant differences in the pharmacokinetic parameters of S-(-)- and R-(+)-OFLX.