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穿心莲提取物和穿心莲内酯与依托考昔在大鼠口服给药后的药代动力学和药效学药物相互作用。

Pharmacokinetic and pharmacodynamic herb-drug interaction of Andrographis paniculata (Nees) extract and andrographolide with etoricoxib after oral administration in rats.

作者信息

Balap Aishwarya, Atre Bhagyashri, Lohidasan Sathiyanarayanan, Sinnathambi Arulmozhi, Mahadik Kakasaheb

机构信息

Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University (BVDU), Pune 411038, India.

Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University (BVDU), Pune 411038, India.

出版信息

J Ethnopharmacol. 2016 May 13;183:9-17. doi: 10.1016/j.jep.2015.11.011. Epub 2015 Nov 17.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Andrographis paniculata Nees (Acanthacae) is commonly used medicinal plant in the traditional. Unani and Ayurvedic medicinal systems. It has broad range of pharmacological effects such as hepatoprotective, antioxidant, antivenom, antifertility, inhibition of replication of the HIV virus, antimalarial, antifungal, antibacterial, antidiabetic, suppression of various cancer cells and anti-inflammatory properties. Andrographolide (AN) is one of the active constituent of the A. paniculata Nees extract (APE). They have been found in many traditional herbal formulations in India and proven to be effective as anti-inflammatory drug

AIM OF THE STUDY

To evaluate the pharmacokinetic and pharmacodynamic (anti-arthritic) herb-drug interactions of A. paniculata Nees extract (APE) and pure andrographolide (AN) with etoricoxib (ETO) after oral co-administration in wistar rats.

MATERIALS AND METHODS

After oral co-administration of APE (200mg/Kg) and AN (60mg/kg) with ETO (10mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of Cmax, tmax, t1/2, MRT, Vd, CL, and AUC were calculated by non-compartment model. Change in paw volume, mechanical nociceptive threshold, mechanical hyperalgesia, histopathology and hematological parameters were evaluated to study antiarthritic activity.

RESULTS

Co-administration of ETO with APE and pure AN decreased systemic exposure level of each compound in vivo. The Cmax, AUC, t1/2 of ETO was decreased whereas Vd and CL of ETO was increased significantly after co-administration of ETO with pure AN and APE. In pharmacodynamic study, ETO alone and ETO+APE (10+200mg/kg) groups exhibited significant synergistic anti-arthritic activity as compared to groups ETO+AN, APE and AN alone.

CONCLUSION

The results obtained from this study suggested that ETO, APE and pure AN existed pharmacokinetic herb-drug interactions in rat which is correlated with anti-arthritic study. Physicians and patients using A. paniculata should have the knowledge about its possible herb-drug interaction with ETO.

摘要

民族药理学相关性

穿心莲(爵床科)是传统尤那尼医学和阿育吠陀医学体系中常用的药用植物。它具有广泛的药理作用,如保肝、抗氧化、抗蛇毒、抗生育、抑制HIV病毒复制、抗疟疾、抗真菌、抗菌、抗糖尿病、抑制多种癌细胞以及抗炎特性。穿心莲内酯(AN)是穿心莲提取物(APE)的活性成分之一。它们在印度的许多传统草药配方中都有发现,并被证明是有效的抗炎药物。

研究目的

评估在Wistar大鼠口服共同给药后,穿心莲提取物(APE)、纯穿心莲内酯(AN)与依托考昔(ETO)之间的药代动力学和药效学(抗关节炎)草药 - 药物相互作用。

材料与方法

在大鼠中口服共同给予APE(200mg/kg)、AN(60mg/kg)与ETO(10mg/kg)后,使用高效液相色谱法测定血浆中的药物浓度。通过非房室模型计算Cmax、tmax、t1/2、MRT、Vd、CL和AUC的主要药代动力学参数。评估爪体积变化、机械性伤害感受阈值、机械性痛觉过敏、组织病理学和血液学参数以研究抗关节炎活性。

结果

ETO与APE和纯AN共同给药降低了体内各化合物的全身暴露水平。ETO与纯AN和APE共同给药后,ETO的Cmax、AUC、t1/2降低,而ETO的Vd和CL显著增加。在药效学研究中,与ETO + AN、APE和单独的AN组相比,单独的ETO组和ETO + APE(10 + 200mg/kg)组表现出显著的协同抗关节炎活性。

结论

本研究获得的结果表明,ETO、APE和纯AN在大鼠中存在药代动力学草药 - 药物相互作用,这与抗关节炎研究相关。使用穿心莲的医生和患者应该了解其与ETO可能存在的草药 - 药物相互作用。

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