Pharmacokinetics of Levofloxacin, a New Fluoroquinolone Agents, after Instillation of 0.5% 14C-levofloxacin Ophthalmic Solution to Pigmented Rats

The pharmacokinetics of levofloxacin (LVFX) was investigated after a single or repeated topical application of 0.5% 14C-LVFX ophthalmic solution to pigmented rats. In the case of repeated application, the ophthalmic solution was instilled 3 times a day for 14 days (total 40 times). 1. The radioactivity in the plasma reached a maximum at 10 minutes after single administration and then decreased with half-life of 0.9 hours. The radioactivity distributed rapidly into various tissues. Radioactivity levels in the peripheral tissues were the highest in the kidney, following by the harderian gland, duodenum, liver and lung. Radioactivity disappeared rapidly from almost all tissues within 24 hours after administration. 2. The radioactivity distributed rapidly to anterior segment, cornea and aqueous humor after a single administration. The decrease of radioactivity was rapid in the absence of melanin, but it was slow in the melanin containing ocular tissues. 3. The radioactivity in the melanin containing ocular tissues gradually increased during repeated administration. However, judging from the increase of radioactive concentration after repeated instillation for 40 days, further repeated instillation would not cause a rapid increase of radioactive concentration in these tissues. 4. Ten minutes after a single administration, the radioactivity in the plasma contained mainly the unchanged form. 5. The excretions of radioactivity in the urine and feces amounted to 44.4 and 55.5% of the dose, respectively, within 96 hours after a single administration.