Pharmacokinetic Interactions of Antihepatotoxic Wedelolactone with Paracetamol in Wistar Albino Rats

Abstract

Eclipta alba. (Linn.) Hassk. (Asteraceae), popularly known as “bhringraj,” is effective against liver damage caused by various hepatotoxins and is used traditionally in Indian phytoformulations. For enhanced in vitro. production of wedelolactone (W), leaves of aseptically germinated seedlings were cultured on Murashige and Skoog's (MS) medium supplemented with plant growth regulators under controlled and standardized chemical and environmental conditions. The wedelolactone was extracted, isolated, purified, chemically characterized, and quantitatively estimated. Rats were divided into four groups of six animals each and given paracetamol (250 mg/kg, p.o.), paracetamol (250 mg/kg, p.o.) with wedelolactone (100 mg/kg, p.o.), paracetamol (250 mg/kg, p.o.) with plant leaves extract (250 mg/kg, p.o.), paracetamol (250 mg/kg, p.o.) with leaf callus extract (250 mg/kg, p.o.), respectively. Blood samples were collected at 1, 2, 3, 4, and 6 h after drug administration, and plasma paracetamol concentration was determined. Pharmacokinetic studies revealed that concomitant administration of wedelolactone with paracetamol does not affect the bioavailability of paracetamol. There was no change in Cmax between paracetamol and paracetamol with wedelolactone, but the Tmax of paracetamol was 2 h in control animals while administration of wedelolactone and extracts with paracetamol resulted in shifting of Tmax from 2 to 3 h without affecting the area under the curve (AUC). Because wedelolactone does not alter the bioavailability of paracetamol significantly and also shows a hepatoprotective effect, its use may be recommended in prolonged paracetamol therapy or paracetamol toxicity.