| 莫西沙星在肺炎大鼠与正常大鼠的血浆及肺组织中药动学比较 |
| 投稿时间：2020-02-04 修订日期：2020-05-16 点此下载全文 |
| 引用本文：成熙,黄月英,李奕.莫西沙星在肺炎大鼠与正常大鼠的血浆及肺组织中药动学比较[J].药学实践杂志,2020,38(4):312~317 |
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| 基金项目:上海市虹口区卫计委医学科研课题重点项目（虹卫1602-10）；解放军第411 医院科研课题基金（2014411YN002） |
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| 中文摘要:目的 莫西沙星（MXF）口服给药在被肺炎链球菌（S.p）感染肺炎大鼠与正常大鼠的血浆及肺组织中药动学比较研究。方法 建立肺炎链球菌肺炎大鼠和正常大鼠模型，莫西沙星42 mg/kg灌胃给药，采用微透析技术对肺炎大鼠及正常大鼠的血液及肺组织取样，用高效液相色谱法测定莫西沙星在各样本中的游离药物浓度，计算药动学参数，进行肺炎大鼠和正常大鼠口服莫西沙星的药动学比较。结果 莫西沙星在正常大鼠及肺炎大鼠血液中的t1/2分别为（5.27±4.38）h、（2.15±0.07）h（P>0.05），Cmax分别为（4.94±0.98）μg/ml、（4.83±0.05）μg/ml（P>0.05），Clast_obs/Cmax分别为0.02±0.03、0.27±0.04（P<0.05），AUC0-t分别为（22.33±2.02）μg/ml·h、（12.88±1.19）μg /ml·h（P<0.05），CL/F 分别为（1.79±0.11）(mg/kg)/(μg/ml)·h、（2.49±0.26）(mg/kg)/(μg/ml)·h（P<0.05）；在正常大鼠及肺炎大鼠肺组织中的Cmax分别为（1.42±0.05）μg/ml、（4.84±0.02）μg /ml（P<0.05），t1/2分别为（1.9±0.63）h、（3.39±0.79）h（P>0.05），AUMC分别为（11.93±5.14）μg/ml·h2、（107.01±25.39）μg/ml·h2（P<0.05），AUC0-t分别为（3.06±1.0）7μg/ml·h、（13.16±0.53）μg /ml·h（P<0.01）。结论 ①在400mg/d剂量条件下，莫西沙星灌胃给药后，血液及肺组织内的游离药物浓度较高，远超过最低抑菌浓度（MIC）和防耐药突变浓度（MPC），可以有效清除肺炎链球菌。②肺炎链球菌感染大鼠肺组织中莫西沙星游离浓度始终高于正常大鼠，Cmax约为正常大鼠的3.4倍，莫西沙星在肺炎大鼠的肺组织穿透率显著高于正常大鼠。 |
| 中文关键词:莫西沙星 肺炎链球菌肺炎 微透析 药动学 |
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| Comparative of pharmacokinetic of moxifloxacin in the plasma and lung tissues of pneumonia rats and normal rats |
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| Abstract:Objective To compare the pharmacokinetics of moxifloxacin (MXF) administered orally in the plasma and lung tissues of rats with pneumonia infected by Streptococcus pneumoniae (S.p) and normal rats.Methods To establish a model of Streptococcus pneumoniae pneumonia rats and normal rats. Moxifloxacin was administered by intragastric administration at 42 mg/kg. Microdialysis technique was used to sample the blood and lung tissues of pneumonia rats and normal rats to determine the free drug concentration of moxifloxacin in each sample, calculate the pharmacokinetic parameters, and compare the pharmacokinetics of oral moxifloxacin in pneumonia rats and normal rats.Results The t1/2 of moxifloxacin in the blood of normal rats and pneumonia rats were (5.27±4.38) h, (2.15±0.07) h (P>0.05), and Cmax were (4.94±0.98) μg/ml, respectively, (4.83±0.05) μg/ml (P>0.05), Clast_obs/Cmax were 0.02±0.03, 0.27±0.04 (P<0.05), AUC0-t were (22.33±2.02)μg/ml·h, (12.88±1.19)μg /ml·h (P<0.05), CL/F are (1.79±0.11)(mg/kg)/(μg/ml)·h, (2.49±0.26)(mg/kg)/(μg/ml)·h (P<0.05); Cmax of lung tissue of normal rats and pneumonia rats were (1.42±0.05) μg/ml, (4.84±0.02) μg/ml (P<0.05), t1/2 are (1.9±0.63)h, (3.39±0.79)h (P>0.05), AUMC are (11.93±5.14)μg/ml·h2, (107.01±25.39)μg/ml·h2 (P<0.05), AUC0-t are (3.06±1.0) 7μg/ml·h, (13.16±0.53)μg/ml·h (P<0.01).Conclusions ① Under the 400 mg/d dose condition, after intragastric administration of moxifloxacin, the concentration of free drugs in the blood and lung tissues is higher, far exceeding the minimum inhibitory concentration (MIC) and anti-drug resistance concentration (MPC), can effectively remove Streptococcus pneumoniae. ②The free concentration of moxifloxacin in the lung tissue of rats infected with Streptococcus pneumoniae is always higher than that of normal rats, and the Cmax is about 3.4 times that of normal rats. The penetration rate of moxifloxacin in lung tissue of pneumonia rats is significantly higher than that of normal rats. |
| keywords:moxifloxacin pneumococcal pneumonia microdialysis pharmacokinetics |
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