warfarin and andrographolide

Andrographolide and warfarin are often used together in clinics in China. However, the herb-drug interaction between andrographolide and warfarin is still unknown.. This study investigates the herb-drug interaction between andrographolide and warfarin in vivo and in vitro.. A sensitive and reliable LC-MS/MS method was developed for the determination of warfarin in male Sprague-Dawley rats plasma, and then the pharmacokinetics of orally administered warfarin (0.5 mg/kg) with or without andrographolide (30 mg/kg/day for 7 days) pretreatment was investigated. In addition, Sprague-Dawley rat liver microsomes incubation systems were used to support the in vivo pharmacokinetic data and investigate its potential mechanism.. The method validation results showed that a sensitive and reliable LC-MS/MS method was developed for the determination of warfarin in rat plasma samples. The pharmacokinetic results indicated that co-administration of andrographolide could increase the systemic exposure of warfarin significantly, including area under the curve (118.92 ± 18.08 vs. 60.58 ± 9.46 μg × h/mL), maximum plasma concentration (3.32 ± 0.41 vs. 2.35 ± 0.25 μg/mL) and t. In conclusion, andrographolide could increase the systemic exposure of warfarin in rats when andrographolide and warfarin were co-administered, and possibly by slowing down the metabolism of warfarin in rat liver by inhibiting the activity of CYP3A4 or CYP2C9.

Topics: Animals; Anticoagulants; Chromatography, Liquid; Diterpenes; Herb-Drug Interactions; Male; Microsomes, Liver; Platelet Aggregation Inhibitors; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Warfarin