Pharmacokinetic and Pharmacodynamic Interaction of Andrographolide and Standardized Extract of Andrographis paniculata (Nees) with Nabumetone in Wistar Rats

Abstract

The aim of the study was to investigate the herb-drug interaction of Andrographis paniculata Nees (Acanthaceae) and Andrographolide (AN) with nabumetone (NAB) in wistar rats. Pharmacokinetic and pharmacodynamic interactions were studied after co-administration of APE and AN with NAB in Wistar rats. In pharmacokinetic studies, significant decrease in Cmax, AUC and AUC of 6-MNA after co-administration with pure AN and APE has been observed. T of 6-MNA has been increased to 2 h from 1.5 h in AN + NAB treated group. Changes in mean residential time, clearance and volume of distribution of 6-MNA in APE + NAB treated group and AN + NAB treated group indicated interference of other components of APE other than AN. In pharmacodynamic study, significant decrease in antiarthritic activity of NAB on concomitant administration with APE and AN has been observed. The study concludes that NAB exhibits pharmacokinetic and pharmacodynamic interactions with APE and AN in rats thus alarms the concomitant use of herbal preparations containing APE and AN with NAB. Further study is needed to understand the mechanism and predict the herb-drug interaction in humans. Copyright © 2016 John Wiley & Sons, Ltd.

Potential pharmacokinetic and pharmacodynamic herb-drug interactions of Andrographis paniculata (Burm. f.) and andrographolide: A systematic review

“…By contrast, another study on HDIs with nabumetone via a pharmacodynamics assay showed that the antiarthritic activity significantly decreased; similarly, several pharmacokinetic profiles (C max , AUC, and T½) decreased (30). The reduction in some of these pharmacokinetic parameters was not supported by a statistically significant increase in volume distribution.…”

“…The pharmacokinetic interaction mechanism involving the CYP1A2 enzyme from APE and AND has also been proven in several anti-inflammatory drugs, such as etoricoxib, nabumetone, and naproxen (28)(29)(30). These drugs are metabolized primarily through the CYP1A2 enzyme activity pathway in mice and other enzymes, such as CYP2A6, CYP2C9, CYPC19, CYP2D6, and CYP3A4, expressed in humans (46)(47)(48)(49).…”

An insight into the pharmacological and analytical potential of Andrographolide

“…Similarly, antiarthritic activity of andrographolide is observed in Wistar rats F I G U R E 5 Schematic diagram of antioxidant activity of andrographolide. AG, andrographolide; MAPK, mitogenactivated protein kinase; AKT, isoform of protein kinase B; mTOR, mechanistic target of rapamycin; EGFR, epidermal growth factor receptor; FasL, Fas ligand; PI3K, phosphoinositide 3-kinases; PDK1, pyruvate dehydrogenase kinase 1; JAK, Janus kinases; STAT3, signal transducer and activator of transcription proteins 3; BCL2, B-cell lymphoma 2 when administered orally in combination with Nabumetone [61]. The anti-inflammatory effect of andrographolide was investigated in hyperglycemia (HG)-induced HUVEC 12 cell lines.…”

“…In an in vitro experiment, andrographolide (50 mg/kg) accelerated apoptosis and autophagy of neutrophil extracellular traps formed during rheumatoid arthritis [60]. Similarly, antiarthritic activity of andrographolide is observed in Wistar rats when administered orally in combination with Nabumetone [61]. The anti‐inflammatory effect of andrographolide was investigated in hyperglycemia (HG)‐induced HUVEC 12 cell lines.…”

Comparative bioavailability studies of binary and ternary solid dispersions of Nabumetone in Wistar albino rats

“…Radiotracer and auto-radiographic methods were also used to study the bio-distribution pattern of 6-MNA and its pharmacokinetic profile (Haddock et al, 1984(Haddock et al, , 1983. Simultaneous determination of 6-MNA and herbal components were also reported using modified HPLC method (Balap et al, 2016). Binary and ternary solid dispersions of NBT prepared by melt-method that exhibited better product characteristics upon evaluation were chosen for in-vivo studies to find out the bioavailability.…”