目的 考察不同给药途径苦参碱注射液在大鼠体内的药动学。方法 20只健康SD大鼠,随机分为两组,分别单剂量腹腔和尾静脉注射15 mg·kg-1的苦参碱注射液。分别于给药前及给药后0.033、0.083、0.167、0.333、0.5、0.75、1、2、3、4、6、8、12 h分别采集静脉血0.3~0.4 mL 。采用LC-MS/MS测定血浆样品中苦参碱的血药浓度,并计算主要的药动学参数。结果 单剂量腹腔和尾静脉注射15 mg·kg-1的苦参碱注射液后AUC0-12分别为(10 166±2 426)和(12 217±2 968) ng·mL-1·h; AUC0-∞分别为(10 230±2 432)和(12 300±3 031) ng·mL-1·h;MRT0-12分别为(1.91±0.41)和(2.14±0.54) h,MRT0-∞分别为(2.01±0.41)和(2.26±0.64) h;t1/2分别为(2.26±0.89)和(2.60±1.25) h,Vd分别为(4 998±2 010)和(6 175±2 540) mL;CL分别为(1 531±315.0)和(1 727±475.6) mL·h-1·kg-1;ρmax分别为(5 246±1 187)和(8 503±1 101) ng·mL-1。腹腔注射的生物利用度为83.21%。结论 比较腹腔和尾静脉注射2种给药途径时苦参碱的药动学参数,AUC、MRT、t1/2和CL均无统计学差异,ρmax和Vd比较具有统计学差异。
Abstract
OBJECTIVE To investigate the pharmacokinetics of matrine injection by different routes of administration. METHODS Twenty healthy SD rats were enrolled in this study. They were randomly divided into two groups and received intraperitoneal and intravenous administration of matrine injection at dose of 15 mg·kg-1 respectively. Blood samples (0.3-0.4 mL) were immediately collected into heparinized tubes before injection and at 0.033, 0.083, 0.167, 0.333, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 h after injection. Plasma sample concentrations were determined by a validated LC-MS/MS method. The pharmacokinetic parameters including AUC0-12, AUC0-∞, MRT0-12, MRT0-∞, t1/2, Vd, CL and ρmax were calculated. RESULTS The main pharmacokinetic parameters for matrine after intraperitoneal and intravenous administration at dose of 15 mg·kg-1 were as follows:AUC0-12 (10 166±2 426), (12 217±2 968) ng·mL-1·h;AUC0-∞ (10 230±2 432), (12 300±3 031)- ng·mL-1·h;MRT0-12 (1.91±0.41), (2.14±0.54) h;MRT0-∞ (2.01±0.41), (2.26±0.64) h; t1/2(2.26±0.89), (2.60±1.25) h;Vd(4 998±2 010), (6 175±2 540) mL;CL (1 531±315.0), (1 727±475.6) mL·h-1·kg-1; ρmax (5 246±1 187), (8 503±1 101) ng·mL-1, respectively. The bioavailability of intraperitoneal administration is 83.21%. CONCLUSION No significant differences were observed in AUC, MRT, t1/2 and CL values of matrine between different administrations except for ρmax and Vd.
关键词
苦参碱注射液 /
LC-MS/MS /
血浆药物浓度 /
药动学 /
给药途径
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Key words
matrine injection /
LC-MS/MS /
plasma concentration /
pharmacokinetics /
administration route
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中图分类号：
R969.1
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参考文献
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脚注
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基金
河北省卫生厅医学科学研究重点课题项目(20100122);河北省中医药管理局科研计划项目(2013161)
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