Phase I clinical study of pazufloxacin mesilate

Abstract

A phase I clinical study of pazufloxacin mesilate (PZFX) was conducted in 52 healthy male adults. The single-dose (drip infusion over 30min) study was started at 50mg, and serially increased to 100, 200, 400, and 500mg.
The multiple-dose study was carried out at doses of 300 and 500mg twice daily and 500 mg 3 times daily, for 5 days. The effect of drip infusion time and combined dosing with probenecid was assessed, and the following results were obtained.
Slightly increased NAG was observed in 2 cases in the 500mg single-and multiple-dose study. No other abnormal subjective or objective findings, physical findings, electrocardiographic findings, or laboratory test values were detected.
Dose-dependent changes were observed in serum levels during the single-dose study with 50, 100, 200, 400, and 500mg of PZFX. The maximum serum levels were observed at 30min, at the end of drip infusion, and were 1.28, 2.68, 4.61, 9.93, and 11.0μg/ml, respectively, with half-lives in serum of 1.74-1.88 hours. Cmax and AUC were proportional to the doses. Urinary excretion rates showed little change with increasing dose, and were 89.5-93.9% at 24hours after administration. The serum levels reached a plateau on day 1 in the multiple-dose study, and no accumlation was observed on the basis of urinary excretion rates. Comparison of 30-and 60-min drip infusion time revealed that the maximum serum levels for 60min was decreased to 80% of the maximum level for 30min. No safety problems were observed with the 1, 000 mg single-dose. Combination with probenecid increased the half-life in blood and decreased the urinary excretion rates. This shows that the mechanism of urinary excretion of PZFX is related to glomerular filtration and tubular absorption.
Thus, PZFX appears to be free of safety problems, and in view of its pharmacokinetics and antimicrobial activity against various organisms, a clinical trials seems warranted.