Phase I Study of Levofloxacin, (S)-(-)-Ofloxacin.

Phase I study of levofloxacin, an optically active isomer of ofloxacin, was conducted in 21 normal healthy male volunteers.In the single-dose studies, levofloxacin was orally administered at doses of 50, 100, and 200mg after breakfast. The serum concentration of levofloxacin peaked at 0.92 to 2.41hr and reached 0.57, 1.22, and 2.04μg/ml, respectively, in a dose-dependent manner. The t1/2 of serum levels were about 4 to 6hr. Approximately 85 to 92% of the dose was excreted unchanged into urine within 48hr and 3.9% into feces within 72hr. The absorption of levofloxacin tended to be more rapid under fasting condition than after meal, whereas the urinary recovery was not altered. The pharmacokinetic profiles of levofloxacin and ofloxacin, determined at a single dose of 200mg, were quite comparable, except for the significant difference in Vd and mean residence time. In the multiple-dose study, levofloxacin was not accumulated on the basis of serum concentrations and urinary recoveries. The salivary to serum concentration ratio of levofloxacin was about 0.7 until 10hr after administration. There was no obvious observation of chiral conversion of (S)-(-)-isomer, levofloxacin, to (R)-(+)-isomer in the body. Levofloxacin was well tolerated.