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甘草提取物与紫杉醇的药草-药物相互作用潜力:大鼠体内药代动力学研究

Herb-Drug Interaction Potential of Licorice Extract and Paclitaxel: A Pharmacokinetic Study in Rats.

作者信息

Ha Yinuer, Wang Tingrui, Li Jianhuang, Li Jun, Lu Ruohuang, Li Jing, Chen Lin, Gan Pingping

机构信息

Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, 410008, China.

Department of Neurology, Binzhou Central Hospital, Binzhou Medical College, Binzhou, 251700, China.

出版信息

Eur J Drug Metab Pharmacokinet. 2020 Apr;45(2):257-264. doi: 10.1007/s13318-019-00593-5.

Abstract

BACKGROUND AND OBJECTIVES

Licorice is the dried roots and rhizomes of Glycyrrhiza uralensis Fisch (Leguminosae), which is often used with paclitaxel to alleviate paclitaxel-induced pain in clinics. However, the herb-drug interaction between licorice and paclitaxel is still unknown. Our study evaluates the effects of oral licorice on the paclitaxel in rats via pharmacokinetic studies.

METHODS

A simple and rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to determine paclitaxel in rat. SD rats were randomly divided into 3 groups of 6 animals each as follows: two groups of rats that were pretreated with a daily gavage of licorice (3 g/kg) for 1 or 14 successive days; Control group that was administered distilled water. All rats were then intravenously administered with paclitaxel (3 mg/kg).

RESULTS

The results showed that 14 days pretreatment of licorice could decrease the area under the curve (AUC) (from 7483.08 ± 528.78 to 6679.12 ± 266.56 mg/L × h) (P < 0.01), and increase the total clearance (CL) (from 0.36 ± 0.02 to 0.39 ± 0.02 L/h/kg) of paclitaxel (P < 0.01). However, a single co-administration of licorice did not significantly alter the pharmacokinetic parameters of paclitaxel, such as AUC (from 7483.08 ± 528.78 to 7201.24 ± 292.76 mg/L × h) (P > 0.05) and CL (from 0.36 ± 0.02 to 0.36 ± 0.01 L/h/kg) (P > 0.05).

CONCLUSIONS

The results will contribute to better use of licorice in the adjunctive therapy and provide information to study the interaction between herbs and chemotherapy.

摘要

背景与目的

甘草是豆科植物乌拉尔甘草的干燥根及根茎,在临床上常与紫杉醇联用,以减轻紫杉醇所致疼痛。然而,甘草与紫杉醇之间的药草-药物相互作用尚不清楚。本研究通过药代动力学研究评估口服甘草对大鼠体内紫杉醇的影响。

方法

建立了一种简单快速的超高效液相色谱-串联质谱法(UHPLC-MS/MS)来测定大鼠体内的紫杉醇。将SD大鼠随机分为3组,每组6只,分组如下:两组大鼠连续1天或14天每日经口灌胃甘草(3 g/kg);对照组给予蒸馏水。然后所有大鼠静脉注射紫杉醇(3 mg/kg)。

结果

结果显示,甘草预处理14天可降低紫杉醇的曲线下面积(AUC)(从7483.08±528.78降至6679.12±266.56 mg/L×h)(P<0.01),并增加紫杉醇的总清除率(CL)(从0.36±0.02升至0.39±0.02 L/h/kg)(P<0.01)。然而,单次联用甘草并未显著改变紫杉醇的药代动力学参数,如AUC(从7483.08±528.78降至7201.24±292.76 mg/L×h)(P>0.05)和CL(从0.36±0.02降至0.36±0.01 L/h/kg)(P>0.05)。

结论

本研究结果将有助于甘草在辅助治疗中的更好应用,并为研究药草与化疗药物之间的相互作用提供信息。

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