Multiple-dose pharmacokinetics and safety of oral amifloxacin in healthy volunteers

The multiple-dose pharmacokinetics and safety of amifloxacin, a new fluoroquinolone antibacterial agent, were evaluated in health 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 liquidh 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 μg/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 μg/ml on day 11 of the study for the 200-, 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 amifloacin 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 μg/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 urinar tract infections.