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甘草提取物对中毒剂量马钱子碱的药代动力学影响

Effects of licorice extract on the pharmacokinetics of brucine in poisoning dose

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【作者】 张敏王超温菁方平飞

【Author】 ZHANG Min;WANG Chao;WEN Jing;FANG Ping-fei;Department of Pharmacy,the Second Xiangya Hospital,Central South University;Institute of Clinical Pharmacy,Central South University;

【机构】 中南大学湘雅二医院药学部中南大学临床药学研究所

【摘要】 目的研究甘草提取物对中毒剂量马钱子碱的药代动力学影响。方法大鼠随机分为模型组、对照组和低、中、高3个剂量实验组,每组8只。模型组腹腔注射马钱子碱40 mg·kg-1;高、中、低3个剂量实验组于马钱子碱腹腔注射后分别给予甘草提取物18,0.45,0.18 g·kg-1;对照组于腹腔注射马钱子碱后立刻给予葡醛内酯60 mg·kg-1。第一次给药后0,8.33×10-2,0.25,0.5,0.75,1,2,3,5,7,9,11,24 h眼眶采血获得大鼠血浆,以HPLC-MS/MS法测定马钱子碱血浆浓度。用DAS软件处理数据,计算各组药代动力学参数。结果模型组马钱子碱的Cmax为(4818.37±665.90)ng·mL-1,AUC0-∞为(6296.73±875.14)ng·h·m L-1,t1/2为(3.25±1.28)h。低剂量实验组马钱子碱的药代动力学未发生明显改变;高、中剂量实验组较模型组Cmax分别降低了19.1%和23.5%;t1/2分别缩短了45.5%和48.5%;平均驻留时间(MRT)分别缩短了44.7%和46.8%(P<0.05)。葡醛内酯处理对马钱子碱药代动力学无明显影响。结论一定浓度范围内,甘草提取物能明显降低马钱子碱的峰浓度和半衰期,这可能是甘草缓解马钱子碱毒性的重要机制。

【Abstract】 Objective To study the effects of licorice extract on the pharmacokinetics profile of brucine.Methods Rats were randomly divided into five groups: model group,control group,low,middle and high dose experimental groups with 8 rats in each group.Rats in model group were treated with brucine 40 mg · kg-1.Rats in low,middle and high dose experimental groups were administrated with 40 mg · kg-1 brucine and then given 0.18,0.45,18 g·kg-1 licorice extract immediately.Rats in control group were given glucurolactone 60 mg · kg-1 immediately after brucine intraperitoneal injection.The rat plasma was obtained at 0,8.33 × 10-2,0.25,0.5,0.75,1,2,3,5,7,9,11,24 h after intraperitoneal injection of brucine.A robust HPLC-MS/MS method was applied to determination of brucine in rat plasma.The pharmacokinetic behavior of brucine was calculated by DAS software.Results The Cmax,AUC0-∞ and t1/2 in model group were(4818.37 ± 665.90) ng · mL-1,(6296.73 ± 875.14) ng·h·mL-1 and(3.25 ± 1.28) h,respectively.There was nearly no variation on the pharmacokinetics of brucine in low dose experimental group.However,the Cmaxin high and middle dose experimental group was decreased by 19.1% and 23.5% compared with model group,and the t1/2 was decreased by 45.5% and 48.5%; themean retention time(MRT) was decreased by 44.7% and 46.8%(P < 0.05).The pharmacokinetics of brucine in control group had no significant effect compared with model group.Conclusion Glycyrrhiza extract can significantly reduce the peak concentration and half-life of brucine in a certain concentration range,which may be an important mechanism for licorice to alleviate the toxicity of brucine.

【关键词】 甘草马钱子碱药代动力学解毒
【Key words】 licoricebrucinepharmacokineticsdetoxification
【基金】 国家自然科学基金资助项目(81473411)
  • 【文献出处】 中国临床药理学杂志 ,The Chinese Journal of Clinical Pharmacology , 编辑部邮箱 ,2017年22期
  • 【分类号】R285.5
  • 【被引频次】10
  • 【下载频次】413
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