Tolerability and pharmacokinetics of antofloxacin hydrochloride after multiple oral dose administration in healthy Chinese male volunteers.
OBJECTIVE
To evaluate the tolerability and pharmacokinetics characteristics of antofloxacin hydrochloride, a fluoroquinolone developed in China, after multiple oral doses in healthy male Chinese volunteers.


METHODS
13 subjects took 300 mg of antofloxacin hydrochloride once daily for 7 days. Safety was evaluated on Days 0, 2, 4 and 8. Blood and urine samples for pharmacokinetics analysis were taken at designated time points. HPLC was used to assay the serum and urine concentration of antofloxacin.


RESULTS
A total of 12 subjects completed the trial and 1 volunteer was dropped because of a skin rash 2 h after the drug was administered. 1 volunteer had a prolonged prothrombin time (PT), another had a serum alanine aminotransferase (ALT) elevation and a third had increases in aspartate aminotransferase (AST) and I(3)-glutamyltransferase (I(3)-GT). No other complaints were reported during the trial. The steady state serum concentration on a daily 300 mg oral dose was obtained at 96 h. The pharmacokinetics parameters at steady state were: t(max)1.19 A+/- 0.59 h, C(max) 4.49 A+/- 0.81 mg/l, C(min) 1.35 A+/- 0.33 mg/l, AUC(ss) 74.74 A+/- 12.58 mg/l A h, C(av) 3.11 A+/- 0.52 mg/l, t(1/2beta) 20.75 A+/- 2.93 h, PTF 102.13 A+/- 23.92%. The urinary elimination of antofloxacin over 120 h after the last dose was approximately 62%. C(max) in steady state was 50% higher compared to data for Day 1 after a single dose administration.


CONCLUSIONS
The results indicated that 300 mg antofloxacin hydrochloride once daily oral administration is safe, but can lead to high drug concentrations. This should be evaluated further.
Xiao
Y
Y
Institute of Clinical Pharmacology, First Hospital, Peking University, #38 Xueyuan Road, Haidian District, Beijing, China. xiaoyonghong@bjmu.edu.cn
Lu
Y
Y
Kang
Z
Z
Hou
F
F
Wang
S
S
Li
T
T
Liu
Y
Y
Xia
Y
Y
D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D002681:China; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D024841:Fluoroquinolones / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D015242:Ofloxacin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C522674:antofloxacin; D015242:Ofloxacin