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左氧氟沙星片及胃漂浮缓释微丸在大鼠体内的药动学比较研究
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| 篇名： | 左氧氟沙星片及胃漂浮缓释微丸在大鼠体内的药动学比较研究 |
| TITLE： | |
| 摘要： | 目的：建立测定大鼠血浆中左氧氟沙星浓度的方法，并比较左氧氟沙星片及胃漂浮缓释微丸在大鼠体内的药动学差异。方法：将SD大鼠随机分为左氧氟沙星片组和左氧氟沙星胃漂浮缓释微丸组，每组6只。分别空腹灌胃相应药物40 mg/kg（以生理盐水为溶剂），并于给药前及给药后0.25、0.5、1、2、4、8、12、24 h自眼眶取血0.3 mL，采用超高效液相色谱法（UPLC）测定大鼠血浆中左氧氟沙星的浓度。色谱柱为Waters Acquity UPLC BEH C18，流动相为0.1％甲酸溶液-乙腈（78 ∶ 22，V/V），流速为0.3 mL/min，检测波长为294 nm，柱温为40 ℃，进样量为2 μL。采用DAS 3.0软件计算两组大鼠的药动学参数，采用F检验考察两者的差异。结果：左氧氟沙星检测质量浓度的线性范围为0.20～20.12 μg/mL，定量下限为0.20 μg/mL，最低检测限为0.04 μg/mL；日内、日间RSD均小于10％，回收率符合2015年版《中国药典》生物样品定量分析的相关要求。大鼠单剂量灌胃左氟氧沙星片及胃漂浮缓释微丸后的平均药-时曲线均符合二室模型，达峰浓度（cmax）分别为（12.13±1.67）、（8.76±1.13）μg/mL，达峰时间（tmax）分别为（0.86±0.15）、（2.48±0.45）h，消除半衰期（t1/2β）分别为（4.67±0.95）、（6.67±1.01）h，药-时曲线下面积（AUC0-t）分别为（42.95±4.21）、（126.48±9.44）μg·h/mL，AUC0-∞分别为（50.66±6.72）、（132.61±10.63）μg·h/mL。与左氧氟沙星片比较，左氧氟沙星胃漂浮缓释微丸的cmax显著降低，tmax、t1/2β、AUC、平均驻留时间均显著延长或升高（P＜0.05）；相对生物利用度为294％。结论：本研究建立的UPLC法操作简便，专属性强，灵敏度、精密度高，可用于大鼠血浆中左氧氟沙星质量浓度的检测及药动学的研究。将左氧氟沙星制成胃漂浮缓释微丸后，其药动学参数变化明显，药物在大鼠体内的滞留时间明显延长，生物利用度显著提高。 |
| ABSTRACT： | OBJECTIVE： To establish a method for the concentration determination of levofloxacin in rat plasma and compare the pharmacokinetic difference between Levofloxacin tablets and gastric floating sustained-release pellets in rats. METHODS： SD rats were randomly divided into Levofloxacin tablets group and Levofloxacin gastric floating sustained-release pellets group， with 6 rats in each group. They were given relevant medicine intragastrically 40 mg/kg （taking normal saline as solvent）， and the blood samples 0.3 mL were collected before medication and 0.25， 0.5， 1， 2， 4， 8， 12， 24 h after medication. The plasma concentration of levofloxacin in rats was determined by UPLC. The determination was performed on Waters Acquity UPLC BEH C18 column with mobile phase consisted of 0.1％ formic acid-acetonitrile （78 ∶ 22，V/V） at the flow rate of 0.3 mL/min. The detection wavelength was set at 294 nm， and column temperature was 40 ℃. The sample size was 2 μL. The pharmacokinetic parameters of rats were calculated by using DAS 3.0 software， and the difference between them were detected by F-test. RESULTS： The linear range of levofloxacin was 0.20-20.12 μg/mL， and limit of quantitation was 0.20 μg/mL. The limit of detection was 0.04 μg/mL. The intra-day and inter-day RSDs were less than 10％. The recoveries were all in line with the related requirements of quantitation analysis of the biological samples stated in 2015 edition of Chinese Pharmacopeia. Average drug concentration-time curves of single dose of Levofloxacin tablets group and Levofloxacin gastric floating sustained-release pellets group were all in line with two-compartment model after intragastric administration. The pharmacokinetic parameters cmax were （12.13±1.67） and （8.76±1.13） μg/mL； tmax were（0.86±0.15） and （2.48±0.45）h； t1/2β were（4.67±0.95） and （6.67±1.01）h； AUC0-t were （42.95±4.21） and （126.48±9.44） μg·h/mL； AUC0-∞ were （50.66±6.72） and （132.61±10.63） μg·h/mL， respectively. Compared with Levofloxacin tablets， cmax of Levofloxacin gastric floating sustained-release pellets were decreased significantly， and tmax， t1/2β， AUC and mean retention time were prolonged or increased significantly （P＜0.05）， and relative bioavailability was 294％. CONCLUSIONS： Established UPLC method is simple， specific， sensitive and precise， and can be used for the determination of levofloxacin concentration in rat plasma and its pharmacokinetic study. After levofloxacin is made into gastric floating sustained-release pellets， pharmacokinetic parameters are changed significantly， retention time is prolonged significantly and bioavailability is improved significantly. |
| 期刊： | 2019年第30卷第10期 |
| 作者： | 邱妍川，钟玲，何静 |
| AUTHORS： | QIU Yanchuan，ZHONG Ling，HE Jing |
| 关键字： | 左氧氟沙星；胃漂浮缓释微丸；超高效液相色谱法；血药浓度；药动学；大鼠 |
| KEYWORDS： | Levofloxacin； Gastric floating sustained-release pellets； UPLC； Plasma concentration； Pharmacokinetics； Rats |
| 阅读数： | 490 次 |
| 本月下载数： | 8 次 |
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