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

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),AUC_(0-∞)为(6296.73±875.14)ng·h·m L^(-1),t_(1/2)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C_(max)分别降低了19.1%和23.5%;t_(1/2)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。

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.