摘要
目的研究左乙拉西坦(LEV)p H敏感鼻用凝胶在大鼠体内的药代动力学。方法用高效液相色谱法测定大鼠血中LEV的浓度。色谱柱为Wondasil C_(18)柱(250.0 mm×4.6 mm,5.0μm),流动相为乙腈-水(11∶89),检测波长为205 nm,内标为甲硝唑。按照体质量将大鼠随机分为实验组和对照组,每组6只。对照组按10.0 mg·kg^(-1)的剂量灌胃给予0.1%LEV溶液;实验组按1.0 mg·kg^(-1)的剂量鼻腔给予LEV pH敏感鼻用凝胶。用3P97药代动力学软件计算主要药代动力学参数。结果实验组和对照组的主要药代动力学参数如下:t_(max)分别为(0.08±0.01)和(0.75±0.10)h,C_(max)分别为(5.22±0.91)和(10.79±2.62)μg·mL^(-1),AUC_(0-t)分别为(9.72±0.99)和(35.10±11.60)μg·mL^(-1)·h,AUC_(0-∞)分别为(10.43±1.37)和(39.54±13.24)μg·mL^(-1)·h。实验组的t_(max)明显小于对照组,差异有统计学意义(P<0.01)。LEV pH敏感鼻用凝胶的相对生物利用度为275.05%。结论LEV p H敏感鼻用凝胶在大鼠体内吸收快、生物利用度高。
Objective To study the pharmacokinetics of levetiracetam(LEV)pH-sensitive nasal gel in rats.Methods The concentrations of LEV in rat plasma were determined by high performance liquid chromatography.The chromatographic analysis was performed on a Wondasil C_(18) reversed phase column(250.0 mm×4.6 mm,5.0μm).The mobile phase consisted of acetonitrile and water(11∶89)and the detection wavelength was set at 205 nm.Metronidazole was used as internal standard.The rats were randomly divided into experimental group and control group with 6 rats in each group.LEV p H-sensitive nasal gel was nasally administered to the experimental group at a dose of 1.0 mg·kg^(-1) and 0.1%LEV solution was given intragastricaly to the control group at a dose of 10.0 mg·kg^(-1).The main pharmacokinetic parameters of LEV in two groups were calculated by 3P97 pharmacokinetic programe.Results The main pharmacokinetic parameters of LEV for the experimental group and control group were as follows:t_(max) were(0.08±0.01)and(0.75±0.10)h,C_(max) were(5.22±0.91)and(10.79±2.62)μg·mL^(-1),AUC_(0-t) were(9.72±0.99)and(35.10±11.60)μg·mL^(-1)·h,AUC_(0-∞) were(10.43±1.37)and(39.54±13.24)μg·mL^(-1)·h,respectively.t_(max) for the experimental group was obviously smaller than that of control group.There was significant difference in t_(max) between experimental and control groups(P<0.01).The relative bioavailability(F_(r))of the drug p H-sensitive nasal gel was found to be 275.05%.Conclusion LEV pH-sensitive nasal gel shows fast absorption and high bioavailability in vivo.
作者
李爽
黄晶
谷福根
LI Shuang;HUANG Jing;GU Fu-gen(School of Pharmacy,Inner Mongolia Medical University,Hohhot 010110,Inner Mongolia Autonomous Region,China;Department of Pharmacy,Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,Inner Mongolia Autonomous Region,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2022年第2期147-150,共4页
The Chinese Journal of Clinical Pharmacology
关键词
左乙拉西坦
pH敏感鼻用凝胶
高效液相色谱
药代动力学
levetiracetam
pH-sensitive nasal gel
high performance liquid chromatography
pharmacokinetics
