目的 探讨牡荆素(vitexin)在Beagle犬血液的毒代动力学规律及组织分布。方法 Beagle犬静脉滴注8、20和50 mg·kg-1剂量的牡荆素,不同时间点采集血液样本,HPLC测定其血浆中药物浓度。结果 Beagle犬静脉滴注“注射用牡荆素”8、20和50 mg·kg-1剂量,在给药d1、d22、d44和d83血药浓度检测显示牡荆素在Beagle犬体内均呈线性方式代谢。其中在50 mg·kg-1剂量下,牡荆素在Beagle犬体内先有显著性蓄积,后蓄积现象消失,且暴露量随给药时间延长而有所减小;在8、20 mg·kg-1剂量下,牡荆素在Beagle犬体内无蓄积现象,且暴露量随给药时间延长而减小。结论 在8、20 mg·kg-1剂量下,Beagle犬静脉滴注“注射用牡荆素”,犬体内无蓄积现象。
Abstract
OBJECTIVE To investigate the toxicokinetic and tissue distribution of vitexin in Beagle dogs. METHODS Beagle dogs were randomly divided into three groups, and received vitexin injection at small, medium and big doses of 50, 20 and 8 mg·kg-1. They were given medicine once a day for consecutive 3 months by intravenous drip. The blood samples of Beagle dogs were drawn at different time points on the first and last day of administration, and concentrations in plasma were detected by HPLC method. RESULTS Intravenous drip the vitexin injection at the doses of 8, 20 and 50 mg·kg-1, the blood concentration of vitexin linearly metabolized in Beagle dogs when given medicine for 1, 22, 44 and 83 d. Vitexin was significantly accumulated in Beagle dogs, and the accumulation was disappeared, and the exposure decreased with the prolonged time at the dose of 50 mg·kg-1; at the dose of 8 and 20 mg·kg-1, vitexin did not accumulate in Beagle dogs, and the exposure decreased with prolonged administration time. CONCLUSION There is no accumulation of repeated drug delivery in the Beagle dog′s body by intravenous drip at the doses of 8 and 20 mg·kg-1.
关键词
牡荆素 /
毒代动力学 /
Beagle犬 /
高效液相色谱法
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Key words
vitexin /
toxicokinetics /
Beagle dogs /
HPLC
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中图分类号：
R965
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参考文献
[1] DONG L Y, CHEN Z W, GUO Y, et al. Mechanisms of vitexin preconditioning effects on cultured neonatal rat cardiomyocytes with anoxia and reoxygenation[J]. Am J Chin Med, 2008, 36(2): 385-397.
[2] DONG L Y, SHAO X, JIANG Q, et al. Effect of vitexin on energy metabolism of experimental rats with myocardial ischemia and protective mechanism[J]. Chin Tradit Herb Drugs(中草药), 2011, 41(7):1378-1383.
[3] DONG L Y, FAN Y F, SHAO X, et al. Effect of vitexin on apoptosis induced by myocardial ischemia-reperfusion injury in rats[J]. Chin Tradit Pat Med(中成药), 2011, 33(6):1041-1044.
[4] WANG Y N, PENG C F, ZHEN Y L, et al. A study of dose-effect relationship between vitexin and puerarin injections on myocardial ischemia/reperfusion injury in rats[J]. Acta Univ Med Anhui(安徽医科大学学报), 2015, 50(3):314-318.
[5] SHAO X, DONG L Y, LI X L, et al. Effects of vitexin on hemodynamics and myocardial oxygen consumption in anesthetized dogs[J]. Anhui Med Pharm J(安徽医药), 2010, 14(9):1001-1004.
[6] XIE H T, HUANG X J, SUN R Y. Introduction of pharmacokinetic software commonly used at home and abroad[J]. Chin J Clin Pharmacol Ther(中国临床药理学与治疗学), 2001, 6(4):289-292.
[7] WU C Z, CHAI J Y, ZHANG W J. Study on pharmacokinetics of vitexin-4″-O-glycoside in rats[J]. Chin Arch Tradit Chin Med(中华中医药学刊), 2017, 35(8):2183-2189.
[8] MA H L, ZHANG D Q, DING L Q, et al. Simultaneous determination of three flavonoids in hawthorn leaves extract by HPLC-MS/MS method and analysis of their pharmacokinetics in plasma of rats[J]. Tianjin J Tradit Chin Med(天津中医药), 2017, 34(4):266-271.
[9] WU C Z, CHAI J Y, ZHANG W J. Pharmacokinetic study of vitexin glucoside in mice in vivo[J]. Chin Arch Tradit Chin Med(中华中医药学刊), 2016, 34(9):2279-2282.
[10] XU L L, WANG F, JIA Q W, et al. Determination of S-pantoprazole sodium in dog plasma by LC-MS/MS and its toxicokinetic study[J]. Chin Pharm J(中国药学杂志), 2017, 52(15):1359-1362.
[11] LI Z G, GAO Z B, GONG A H, et al. Pharmacokinetic study of ocotillol in rats by LC-MS/MS[J]. Chin Pharm J(中国药学杂志), 2018, 53(9):749-754.
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脚注
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基金
科技部重大新药创制国家科技重大专项资助(2017ZX09301025)
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