摘要
目的观察氨溴索对左氧氟沙星在大鼠血浆、肺组织、支气管液中分布的影响。方法 108只大鼠随机分为实验组和对照组,实验动物均按50 mg·kg^(-1)灌服左氧氟沙星,实验组同时加服氨溴索15 mg·kg^(-1)。于给药后0.08、0.17、0.5、1、2、4、8、12、24 h各时间点,两组分别处死大鼠6只,收集血样,制备血浆,并于给药后0.5、1、8、24 h处死动物分别采集肺组织和支气管液(BLF),高效液相色谱法检测血浆、肺组织和BLF中左氧氟沙星的质量浓度,3p97软件计算药动学参数,并进行统计学分析。结果实验组和对照组大鼠口服左氧氟沙星的血浆药物质量浓度-时间曲线符合二室模型,药动学参数t_(max)分别为(0.16±0.07)h和(0.15±0.04)h,ρ_(max)分别为(7.77±0.69)mg·L^(-1)和(7.34±0.67)mg·L^(-1),t_(1/2β)分别为(6.85±0.44)h和(6.55±0.90)h,AUC_(0-t)分别为(28.80±3.75)mg·h·L^(-1)和(28.23±3.43)mg·h·L^(-1),组间无显著差异(P>0.05),BLF中左氧氟沙星质量浓度也无显著差异(P>0.05),但肺组织中各时间点药物浓度有增高(P<0.05)。结论氨溴索对大鼠口服左氧氟沙星后药动学和BLF药物质量浓度无明显影响,但可以显著增加左氧氟沙星在肺组织中的质量浓度。
AIM To examine the effects of ambroxol on levofloxacin distribution in plasma, lung and bronchial fluid in rats. METHODS One hundred and eight rats were randomly divided into experiment group and control group. Rats were orally administrated with levofloxacin （50 mg .kg^-1） as control group. In the experiment group, rats received both levofloxacin （50 mg .kg^-1） and ambroxol （15 mg.kg^-1）. Blood samples （n ： 6） were harvested at 0.08, 0.17, 0.5, 1, 2, 4, 8, 12 and 24 h. Bronchial lavage fluid （BLF） and lung samples were collected at 0.5, 1, 8 and 24 h. Drug mass concentrations in plasma, lung and BLF were determined by HPLC and pharmacokinetic parameters were calculated with 3p97 software. RESULTS The plasma mass concentration curves of levofloxacin after oral administration fitted a two- compartments model in both groups. Concentrations of levofloxacin in BLF were comparable between two groups. No significant differences of pharmacokinetic parameters were observed between two groups, such as tmax： （0.16 ＋ 0.07） h and （0.15 ± 0.04） h, pmax： （7.77 ± 0.69） mg.L^-1 and （7.34 ± 0.67） mg.L^-1, t1/2β： （6.85 ± 0.44） h and （6.55 ± 0.90） h, AUC0-t： （28.80 ± 3.75） mg.h.L^-1 and （28.23 ＋ 3.43） mg.h.L^-l （P 〉 0.05）. However, the mass concentrations of levofloxacin in lung tissues were significantly higher in the experiment group than those in the control group （P 〈 0.05）. CONCLUTION The combined administration of ambroxol significantly enhanced the mass concentration of levofloxacin in lung, without the alteration of pharmacokinetics and the levels of levofloxacin in bronchial in rats.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2013年第10期789-793,共5页
Chinese Journal of New Drugs and Clinical Remedies
关键词
左氧氟沙星
氨溴索
大鼠
药动学
色谱法
高压液相
levofloxacin
ambroxol
rats
pharmacokinetics
chromatography, high pressure liquid
