Herb-Drug Interaction Potential of Licorice Extract and Paclitaxel: A PharmacokineticStudy in Rats.

Abstract

Licorice is the dried roots and rhizomes of Glycyrrhiza uralensis Fisch (Leguminosae), which is often used with paclitaxel to alleviate paclitaxel-induced pain in clinics. However, the herb-drug interaction between licorice and paclitaxel is still unknown. Our study evaluates the effects of oral licorice on the paclitaxel in rats via pharmacokinetic studies. A simple and rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to determine paclitaxel in rat. SD rats were randomly divided into 3groups of 6 animals each as follows: two groups of rats that were pretreated with a daily gavage of licorice (3g/kg) for 1 or 14 successive days; Control group that was administered distilled water. All rats were then intravenously administered with paclitaxel (3mg/kg). The results showed that 14days pretreatment of licorice could decrease the area under the curve (AUC0-t) (from 7483.08 ± 528.78 to 6679.12 ± 266.56mg/L × h) (P < 0.01), and increase the total clearance (CL) (from 0.36 ± 0.02 to 0.39 ± 0.02L/h/kg) of paclitaxel (P < 0.01). However, a single co-administration of licorice did not significantly alter the pharmacokinetic parameters of paclitaxel, such as AUC0-t (from 7483.08 ± 528.78 to 7201.24 ± 292.76mg/L × h) (P > 0.05) and CL (from 0.36 ± 0.02 to 0.36 ± 0.01L/h/kg) (P > 0.05). The results will contribute to better use of licorice in the adjunctive therapy and provide information to study the interaction between herbs and chemotherapy.