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

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• 作者：Aishwarya Balap^a ; Bhagyashri Atre^b ; Sathiyanarayanan Lohidasan^a ; ^{pharmsathiya@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Arulmozhi Sinnathambi^b ; Kakasaheb Mahadik^a ; ^{krmahadik@redifffmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AN ; Andrographolide ; ANOVA ; Analysis of variance ; APE ; Andrographis Paniculata Nees Extract ; AUC0&ndash ; &infin ; Area under plasma concentration&ndash ; time curve extrapolated to infinity ; AUClast ; Area under plasma concentration&ndash ; time curve from zero to last time point ; AUMC0&ndash ; &infin ; Area under the concentration time (c× ; t) versus time (t) curve for extrapolated to infinity ; AUMClast ; Area under the concentration time (c× ; t) versus time (t) curve for last time point ; CL ; Pl
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：13 May 2016
• 年：2016
• 卷：183
• 期：Complete
• 页码：9-17
• 全文大小：1499 K

文摘

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 (200 mg/Kg) and AN (60 mg/kg) with ETO (10 mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of C_max, t_max, t_1/2, 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 C_max, AUC, t_1/2 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+200 mg/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.