Abstract
A phase I clinical study on pazufloxacin(PZFX) was conducted in 23 healthy male adults. The single-dose study was started from 20mg in the fasting state, and serially increased to 50, 100, 200 and 400mg. The effect of food intake was investigated by same volunteers in the single-dose study with 200mg. The multiple-dose study was carried out a total of 19 times at a single dose of 300mg given 3 times a day after meals for 7 days. The following results were obtained.
Rash was observed in both the brachia and the inside of a thigh in 1 patient on day 7 in the multiple-dose study. This disappeared within 1 week after withdrawal, showing no abnormal laboratory test values. No other abnormal subjective or objective findings, physical findings, electrocardiographic findings or laboratory test values were observes.
Dose-depentdent changes were observed in the blood levels during the single-dose study in the fasting state with 100, 200 and 400mg of PZFX. The average maximum blood levels were observed between 0.58 and 0.94 hour, 0.944, 2.975 and 4.512 μg/ml, respectively, with half-lives in blood of 2.01-2.48hours. Cmax and AUC were proportionally related with the dose. Urinary excretion rates showed little change with increasing dose, and were 81.2-85.1% at 24 hours after administration. In the study of effects of food intake, Cmax, at 2.97μg/ml in the fasting state, was higher than the postprandial Cmax, 2.02μg/ml, but the postprandial Tmax of 1.20 hours was longer than the fasting value, 0.576 hours. T1/2in the fasting state was 2.27 hours, longer than the postprandial value(1.88 hours); however, AUC were almost the same in both states. The blood levels reached a plateau on day 1 in the multiple-dose study, 3 times a day for 7 days, and no accumulation was observed on the basis of urinary excretion rates.
Thus, PZFX is considered to have no problem with safety, and, taking into consideration its pharmacokinetics and the microbial activity against various organisms, its clinical evaluation seems warranted.
