The multiple-dose pharmacokinetics and safety of
amifloxacin, a new
fluoroquinolone antibacterial agent, were evaluated in healthy male volunteers.
Amifloxacin was administered orally at 200, 400, or 600 mg every 12 h (q12h) and 400, 600, or 800 mg every 8 h (q8h) for 10 days. An additional dose was administered on day 11. Concentrations of
amifloxacin in plasma and urine were measured on days 1, 5, and 11 by high-performance liquid chromatography. Steady-state
amifloxacin concentrations were reached by day 5. Mean +/- standard deviation maximum observed
amifloxacin concentrations in plasma were 2.52 +/- 1.12, 4.98 +/- 1.44, 5.40 +/- 2.02, 4.59 +/- 2.17, 6.53 +/- 2.44, and 8.01 +/- 3.00 micrograms/ml after the initial dose and 2.30 +/- 0.98, 5.41 +/- 0.74, 8.05 +/- 1.68, 6.87 +/- 2.81, 9.53 +/- 0.50, and 11.9 +/- 1.92 micrograms/ml on day 11 of the study for the 200-, 400-, and 600-mg q12h and 400-, 600-, and 800-mg q8h regimens, respectively.
Amifloxacin was rapidly absorbed, as evidenced by the mean time to the maximum observed
amifloxacin concentration of 0.98 h. Mean values for the terminal
amifloxacin half-life in plasma ranged from 3.58 to 5.78 h. Mean
amifloxacin concentrations in urine on day 11 in samples collected 0 to 2 h after dosing were 105, 417, 376, 336, 518, and 464 micrograms/ml for the 200-, 400-, and 600-mg q12h and 400-, 600-, and 800-mg q8h regimens, respectively. The mean amount of the dose excreted in the urine as
amifloxacin was 53.9%.
Amifloxacin was generally well tolerated, although there was a tendency for the subjects who received
amifloxacin to experience more gastrointestinal, central nervous system, and cutaneous complaints than did those who received placebo. Clinically significant adverse reactions, including
pruritus and
transaminase elevations, occurred only at doses of 1,200 mg/day or above. Clinical and pharmacokinetic data suggest that orally administered
amifloxacin may have utility in the treatment of
urinary tract infections.