Pharmacokinetic analysis and tissue distribution of andrographolide in rat by a validated LC-MS/MS method

Abstract

Context: Andrographis paniculata (Burm.f.) Nees (Acanthaceae) is widely used in tribal medicine in India and some other countries for multiple clinical applications. It contains andrographolide (AG) (diterpenoid lactone), a major phytomarker which probably accounts for its medicinal properties.Objective: This study investigates the site-specific distribution of AG in different tissues of rats and its pharmacokinetic parameter evaluation by using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Materials and methods: A simple and sensitive LC-MS/MS method has been developed and validated to quantify the presence of AG in plasma and various tissues of rat following oral administration of A. paniculata extract and AG in a dose of 133.33 and 100 mg/kg/day, respectively, for four weeks.Results: The present study showed that the highest concentration of AG was in kidney (156.12 ng/g) followed by liver, spleen and brain while almost same concentration was found in heart and lung. The apparent C max , T max , elimination half-life and total exposure (AUC 0-) were 115.81 ng/ml, 0.75, 2.45 and 278.44 ngh/ml, respectively. Conclusion: This was an attempt to determine the presence of AG (a known biomarker) in tissues such as kidney, heart, lungs, brain and plasma of rats using a validated LC-MS/MS method. Furthermore, the observed reduced concentration in plasma and various tissues from 1 to 8 h might be attributed to relatively rapid elimination or distribution of AG from the central compartment.

Dry state microcrystals stabilized by an HPMC film to improve the bioavailability of andrographolide

“…Interestingly, there was an unexpected finding that double peaks appeared in both plasma concentration-time curves, which is not consistent with previous reports (Bera et al, 2014;Xu et al, 2009;Zhang and Fan, 2012;Zhao et al, 2013). This may be attributed to the fact that the metabolism of ADG is very different among different species.…”

Andrographolide suppresses proliferation of human colon cancer SW620 cells through the TLR4/NF-κB/MMP-9 signaling pathway

“…The molecular formula of andrographolide is C 20 H 30 O 5 and it is one of the active components of A. paniculata extract, comprising up to 1.84% of the extract (10,11). Andrographolide has been produced as a raw material with antipyretic and analgesic effects (12).…”

Pharmacokinetics and Anti-Inflammatory Activity of Andrographolide in Rats

“…Mean apparent volume of distribution (Vd area : 6.9 ± 0.38 L/kg) of andrographolide following intramuscular administration in rats was found higher than reported following oral administration (0.04 ± 0.005 and 0.06 ± 0.1) of Andrographis paniculata extract (20 and 200mg/kg) in rats respectively (Pannossian et al, 2000). This finding was supported by higher value of AUC (13.7 ± 0.47 g.h/mL) in comparison with findings reported following oral administration of andrographolide (30mg/kg) and ethanolic extract of Andrographis paniculata (20 and 200 mg/kg) in rats respectively (Bera et al, 2014;Pannossian et al, 2000). Moreover, low plasma protein (55%) binding efficiency of drug (Dey et al, 2013) can also contribute high distribution of andrographolide in rats.…”

“…The mean absorption half-life (t ½Ka : 0.60 ± 0.07 h)of andrographolidein rats following single dose intramuscular administration in the present study was in accordance to absorption half-life (0.69 ± 0.3 h) reported following oral administration of ethanolic extract of Andrographis paniculata (20 mg/kg) in rats (Pannossian et al, 2000). The elimination half-life (t 1/2β : 1.33 ± 0.10 h) of andrographolide in rats following single dose intramuscular administration in present study was found lower than elimination half-life (2.45 h, 3.1 ± 0.2 h and 2.5 ± 0.1 h;) reported following oral administration of andrographolide (30mg/kg) and ethanolic extract of Andrographis paniculata (20 and 200 mg/kg) in rats respectively (Bera et al, 2014;Pannossian et al, 2000). Mean apparent volume of distribution (Vd area : 6.9 ± 0.38 L/kg) of andrographolide following intramuscular administration in rats was found higher than reported following oral administration (0.04 ± 0.005 and 0.06 ± 0.1) of Andrographis paniculata extract (20 and 200mg/kg) in rats respectively (Pannossian et al, 2000).…”

“…Similarly, C max (3.0  0.6 g/mL at 1.67 h) was reported following oral administration of Andrographis paniculata extract (200 mg/kg) in rats (Pannossian et al, 2000). However, the lower values of C max (1.27  0.2 g/mL at 2.4 h, 0.115 g/mL at 0.75 h and 1,62  0.11g/mL at 0.99 h) were reported following oral administration of Andrographis paniculata extract (20 mg/kg), andrographolide (30mg/kg) and andrographolide tablet (10mg/kg) in rats respectively (Pannossian et al, 2000;Suo et al, 2007;Bera et al, 2014).…”