Healthy supplements of silymarin and aqueous extract of Salvia miltiorrhiza on the pharmacokinetic interaction of lamivudine in rats

Abstract

Silymarin and Salvia miltiorrhiza are commonly used in various functional foods, daily herbal health supplements and food supplements for the treatment and prevention of liver disease. The aim of this study was to evaluate the herbal–drug interactions of silymarin and the aqueous extract of S. miltiorrhiza (AESM) on the pharmacokinetics of lamivudine in rat plasma as measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). A rapid and sensitive LC–MS/MS method was developed and validated according to the Food and Drug Administration (FDA) guidelines. Experimental rats were divided into the following four parallel groups: (1) lamivudine (10 mg/kg, i.v.) alone as a control group, (2) lamivudine (10 mg/kg, i.v.) + pretreated with silymarin (0.5 g/kg/day, p.o., daily for 5 days), (3) lamivudine (10 mg/kg, i.v.) + pretreated with AESM (1.0 g/kg/day, p.o., daily for 5 days), and (4) lamivudine (10 mg/kg, i.v.) + pretreated with silymarin (0.5 g/kg/day, p.o., daily for 5 days) + AESM (1.0 g/kg/day, p.o., daily for 5 days). The pharmacokinetic results demonstrate that AESM significantly increased lamivudine half-life (t1/2), area-under concentration curve (AUC), and mean residence time (MRT), while clearance (CL) decreased. Thus, this study provides preclinical information regarding the pharmacokinetic interactions between lamivudine and the herbal health supplements.

Keywords

• Lamivudine
• Silymarin
• Salvia miltiorrhiza
• Herbal–drug interaction
• Pharmacokinetics