Abstract
The metabolism after oral administration of grepafloxacin (GPFX) or [14C] GPFXwas investigated in rats, monkeys and humans.
1. The metabolites of GPFX identified using human urine and rat urine and bile were two GPFX glucuronic acid conjugates (3-glucuronide and 4'-glucuronide), one GPFX sulfate conjugate (4'-sulfate), four metabolites with a metabolized 3-methylpiperazinyl ring (DM-1704, DM-1705, DM-1706 and DM-1725) and two 5-hydroxymethyl-type metabolites (DM-1722 and DM-1723).
2. The main metabolite of GPFX in human plasma was DM-1705. The metabolites excreted in urine during the period of 0-72 hours after dosing were 3-glucuronide (4.0% of the administered dose), 4'-glucuronide (3.5%), DM-1705 (3.0%), DM-1704 (1.3%), 41-sulfate (1.0%) and DM-1706 (0.2%). The metabolites excreted in feces during the period of 0-72 hours after dosing were DM-1705 (2.6%), DM-1704 (2.1%), DM-1725 (1.9%), DM-1706 (1.8%) and 4'-sulfate (1.3%).
3. The main metabolite of GPFX in plasma in both male and female rats was 3-glucuronide. The main metabolite in urine was DM-1723 in male rats and 3-glucuronide in female rats. The main metabolite in feces in both sexes was 4'-sulfate. The main metabolite in bile in male rats was 3-glucuronide. GPFX in male rat lungs accounted for more than 90.5% of the total radioactivity in the lungs, and other metabolite was detected.
4. The main metabolites in monkey plasma, urine and feces were DM-1704, DM-1704 and 4'-sulfate, respectively.
