1999 Volume 47 Issue Supplement1 Pages 65-75
We investigated the pharmacokinetics of pazufloxacin mesilate (PZFX mesilate), the methanesulfonic acid salt of pazufloxacin (PZFX), after intravenous administration to experimental animals and obtained the following results.
1. The half-life of PZFX after a single intravenous administration of PZFX mesilate at a dose equivalent to 5 mg of PZFX/kg was 4.5 h in dogs, 1.0 h in rabbits, 0.88 h in rats, and 0.23 h in mice. No obvious differences among animal species were observed in serum levels of PZFX at 5 min after intravenous administration of PZFX mesilate, and the values were within the 4.77-6.83μg/ml range in all animals.
2. In rats, PZFX was rapidly distributed to various tissues except brain after a single intravenousadministration of PZFX mesilate. Particularly high distribution was found in the kidney, whilethe levels in other tissues were comparable to the serum levels. The PZFX concentrations in all tissues declined rapidly.
3. Urinary excretion rates of PZFX mesilate as the active form within 24 hours after intravenous administration were 44.7 % of the dose in mice, 74.3 % in rats, 54.9 % in rabbits, and 56.6% in dogs. The biliary excretion rate of PZFX mesilate as active form was 2.2% within 24 hours after intravenous administration in rats.
4. A dose-proportionality study was conducted with intravenous administration of PZFX mesilate at doses equivalent to 5 to 100 mg of PZFX/kg in rats. The AUCs were linearly proportional to the doses, and the urinary excretion rates were almost constant at these doses.
5. There were no significant differences in the serum levels or the urinary excretion rates after multiple administration twice daily for 6 days compared with the data after a single administration.
6. In rats with D-galactosamine-induced liver dysfunction the rate of decrease of the serum levels was slightly delayed, but there were no significant differences in the serum levels or the urinary excretion rates compared with those of normal rats. By contrast, in rats with HgCl2-induced kidney dysfunction the serum levels were significantly increased and urinary excretion was significantly decreased.
7. No antimicrobially active compounds except PZFX were detected by bioautography in urine samples of mice, rats, rabbits, or dogs.
