Pharmacokinetics of antofloxacin hydrochloride in healthy male subjects after multiple intravenous dose administration

Abstract

1. The purpose of the study was to evaluate pharmacokinetic characteristics of antofloxacin hydrochloride, a new fluoroquinolone antibiotic, during a multiple, intravenous dosing regimen.

2. Twelve healthy, Chinese male volunteer subjects were each given 300 mg of antofloxacin by intravenous infusion once daily for 7 days. Blood and urine samples were taken at designated time points for analysis of antofloxacin concentration by high-performance liquid chromatography (HPLC). Safety and tolerability were assessed by evaluation of subject complaints, vital signs, electrocardiograms, electroencephalograms, clinical chemistry parameters, haematology and urinalysis and prothrombin time.

3. The serum steady concentration of antofloxacin was obtained in 96 h after the administration of a daily intravenous dose of 300 mg of the drug. In the present study, the following pharmacokinetic parameters after 7 days of treatment with antofloxacin were determined to be: C_max 3.81 ± 0.66 mg/L, C_min 0.85 ± 0.19 mg/L, AUC_0–24 60.51 ± 8.30 mg/L·h, C_av 2.52 ± 0.35 mg/L, PTF 87.45 ± 3.37%, t_1/2β 20.34 ± 1.88 h. The C_max and AUC_0–24 after 7-day treatment were both higher than after the first dose (by 43% and 110%, respectively). The cumulative urinary elimination of antofloxacin within 96 h after the last dose was about 56%.

4. During the study, there were neither subject complaints nor significant adverse clinical findings.

5. Antofloxacin, administered intravenously as a single, daily 300 mg dose for 7 days, demonstrated favourable pharmacokinetic characteristics and tolerability. The results of this study indicate that antofloxacin hydrochloride is suitable for further clinical study.

Keywords::

• Antofloxacin hydrochloride
• multiple-dose pharmacokinetics
• intravenous
• healthy male volunteers