1995 Volume 43 Issue Supplement2 Pages 132-142
The effect of pazufloxacin(PZFX), a synthetic new quinolone antimicrobial agent, on blood glucose levels and several factors affected to them was evaluated in rats using single or 28-days repeated administration. The following results were obtained;
1. In preliminary assessment of the evaluation model in rats, the assay system for blood glucoseregulating factors (insulin, etc.) was judged as reliable, since it produced results in an oral glucose loading test consistent with those reported elsewhere. It was found possible to narrow down diurnal variations by introducing fasting from 21: 00 of the previous day. Human test kits used for the measurement of insulin and thyroid hormones were usable for the measurement of these parameters in the blood of rats.
2. In the single administration test, PZFX was found to reach saturation in the blood at a dose of 1200 mg/kg, which corresponded to 100 times the proposed clinical dose. However, no abnormal or specific changes were noted in any biochemical parameters(such as blood glucose, insulin, glucagon and thyroid hormones etc.) or in histopathological examination of the pancreas (islets of Langerhans).
3. In the repeated administration test, a dose of 600 mg/kg(approximately 50 times the proposed clinical dose) repeated once daily for 28 days inhibited body weight gain from the second day until the end of administration. This dose was thus estimated to be high enough to induce toxicity.
4. In the repeated administration test, insulin level tended to increase on the final day of administration. Blood glucose level underwent no change. This seemed to be a phenomenon not associated with the drug. No abnormal or specific changes were detected in other biochemical parameters or in histopathological examination of the pancreas (islets of Langerhans).
The present test results combined with results of earlier toxicity tests suggest that it is unlikely that PZFX exerts the effect on blood glucose levels and blood glucose-regulating factors.
