Pharmacokinetic and Pharmacodynamic Interaction of Andrographolide with Meloxicam in Wistar Rats

Abstract

Aim of the study: The primary aim of this study was to evaluate the possible pharmacokinetic and pharmacodynamics (anti-inflammatory) herb-drug interaction of Andrographolide (AN) with meloxicam (Melx) in Wistar rats. Materials and methods: A sensitive and validated RP-HPLC method was developed for the simultaneous estimation of AN and Melx in rat plasma. The oral administration of AN (60mg/kg), Melx 1.55mg/kg) and co-admin group in male-Wistar rats were given. The plasma drug concentration was evaluated using the RP-HPLC method and the pharmacokinetic parameters such as Cmax, Tmax, MRT, T½, CL, Vd, and AUC were calculated. Pharmacodynamic parameters such as Change in paw volume, mechanical hyperalgesia, and mechanical nociceptive threshold were evaluated for predicting the herb-drug interaction. Results: In the pharmacokinetic study there was a considerable increase in the Cmax, Tmax, MRT, and T½ of the co-admin (AN+Melx) group when compared with the individually administered groups (AN, Melx). On the contrary, there was a significant reduction in the clearance, whereas Vd remains unaffected. In pharmacodynamics studies, co-admin (AN+Melx) groups were showing a significant increase in the anti-inflammatory activity against the disease control group when compared with the individually drug administered groups (AN, Melx). Conclusion: The results of this study revealed that the co-admin group exhibited herb-drug interactions by giving a twofold reduction of inflammation when compared with the individually drug administered groups. Medical practitioners and patients should get awareness about the potential HDI's of AN with Melx during the concomitant administration of both drugs to avoid undesirable side effects and drug-related toxicities.