Abstract
The absorption, distribution and excretion of radioactivity after single and repeated oral administrations of [14C] grepafloxacin (GPFX) at 40 mg/kg were investigated in rats.
1. The blood concentration of radioactivity after single oral administration in fasted male rats reached a maximum at 1 hour, indicating rapid absorption. The concentration in fasted rats was higher than that in non- fasted rats. There was no delay in the elimination of radioactivity after repeated administration.
2. The concentrations of radioactivity in almost all tissues after single oral administration in fasted male rats reached a maximum at 0.5-2 hours. The concentrations in almost all tissues were higher than the plasma concentration, indicating high tissue distribution. No radioactivity was detected in almost any tissues at 96 hours after the final dose of the repeated administration. This finding was similar to the results of whole-body autoradiograms.
3. There were no sex differences in the pharmacokinetics of [14C] GPFX.
4. The in vitro binding rates of [14C] GPFX to rat, rabbit and human plasma were 38%-52%, indicating no concentration- dependency. The in vivo binding rates of radioactivity to rat plasma were 41.8%-43.0%, similar to the in vitro binding rates.
5. The administered radioactivity was primarily excreted in the feces via the bile. It was also suggested that entero-hepatic circulation was likely to be observed. There were no changes in the excretion of radioactivity during repeated administration.
6. The radioactivity was primarily excreted in the urine in bile duct-ligated male rats.
7. Placental transfer was suggested in pregnant rats. High distribution in the milk was also observed in lactating rats.
8. Radioactivity remained in the hair and eyeballs at 168 hours after administration in pigmented rats.
