盐酸安妥沙星在健康男性志愿者中单次和多次口服给药的药代动力学研究。

Pharmacokinetic study of single and multiple oral dose administration of antofloxacin hydrochloride in healthy male volunteers.

机构信息

Institute of Clinical Pharmacology, First Hospital, Peking University, Beijing 100191, China.

出版信息

Chin Med J (Engl). 2011 Jan;124(2):242-5.

Abstract

BACKGROUND

A new fluroquinolone antibacterial agent, antofloxacin hydrochloride, developed in China, is an 8-NH(2) derivant of levofloxacin. The purpose of the study was to evaluate the pharmacokinetic characteristics of single and multiple oral doses of antofloxacin hydrochloride in Chinese healthy male volunteers.

METHODS

An open-label, non-randomized, single and multiple dose clinical trial was conducted. In single dose study, 12 subjects took 200 mg antofloxacin hydrochloride. In multiple dose study, 12 subjects took antofloxacin hydrochloride 400 mg once on day 1 and 200 mg once daily from day 2 to day 7. HPLC was used to assay the serum and urinary concentrations of antofloxacin.

RESULTS

In single dose study, the maximum concentration of drug in serum (C(max)), the time to reach C(max) (T(max)), and the area under the serum concentration-time curve (AUC (0-∞)) of antofloxacin were (1.89 ± 0.65) mg/L, (1.29 ± 0.26) hours, and (25.24 ± 7.26) mg×h(-1)×L(-1), respectively. Accumulating elimination rate of antoflocaxin from urine within 120 hours was 39.1%. In multiple dose study, blood concentration of antofloxiacin achieved stable state on day 2 after dosing. The minimum concentration drug in serum (C(min)), AUCss, mean concentration of drug in serum (C(av)), and degree of fluctuation (DF) were (0.73 ± 0.18) mg/L, (47.59 ± 7.85) mg×h(-1)×L(-1), (1.98 ± 0.33) mg/L, and 1.74 ± 0.60, respectively. On day 7 after dosing, T(max), C(max), and AUC (0-∞) was (1.14 ± 0.50) hours, (2.52 ± 0.38) mg/L, and (48.77 ± 8.44) mg×h(-1)×L(-1), respectively. Accumulating elimination rate of antofloxaxin from urine within 120 hours after the last dosing was 60.06%.

CONCLUSIONS

The regimen of 400 mg loading dose given on the first treatment day and then 200 mg dose once daily results in satisfactory serum drug concentration.

摘要

背景

盐酸安妥沙星是我国自行研制开发的新型氟喹诺酮类抗菌药，为左氧氟沙星的 8-位氨基衍生物。本研究旨在评价盐酸安妥沙星在健康中国男性志愿者中单、多次口服给药的药代动力学特征。

方法

采用开放、非随机、单、多次给药临床试验设计。单次给药研究中，12 名受试者单次口服盐酸安妥沙星 200mg；多次给药研究中，12 名受试者于第 1 天单次口服盐酸安妥沙星 400mg，第 2 天起每日单次口服 200mg。采用 HPLC 法测定血清和尿液中安妥沙星浓度。

结果

单次给药研究中，盐酸安妥沙星的血清峰浓度（Cmax）、达峰时间（Tmax）和血清浓度-时间曲线下面积（AUC（0-∞））分别为（1.89±0.65）mg/L、（1.29±0.26）h 和（25.24±7.26）mg·h·L-1，尿液中药物累积排泄率在 120h 内为 39.1%。多次给药研究中，受试者于第 2 天开始达到稳态血药浓度。第 2 天的最低血药浓度（Cmin）、AUCss、平均血药浓度（Cav）和波动度（DF）分别为（0.73±0.18）mg/L、（47.59±7.85）mg·h·L-1、（1.98±0.33）mg/L和 1.74±0.60。第 7 天的 Tmax、Cmax和 AUC（0-∞）分别为（1.14±0.50）h、（2.52±0.38）mg/L 和（48.77±8.44）mg·h·L-1，尿液中药物累积排泄率在末次给药后 120h 内为 60.06%。