Herb–Drug Interaction Potential of Licorice Extract and Paclitaxel: A Pharmacokinetic Study in Rats

Background and Objectives 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. Methods 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 3 groups of 6 animals each as follows: two groups of rats that were pretreated with a daily gavage of licorice (3 g/kg) for 1 or 14 successive days; Control group that was administered distilled water. All rats were then intravenously administered with paclitaxel (3 mg/kg). Results The results showed that 14 days pretreatment of licorice could decrease the area under the curve (AUC 0– t ) (from 7483.08 ± 528.78 to 6679.12 ± 266.56 mg/L × h) ( P < 0.01), and increase the total clearance (CL) (from 0.36 ± 0.02 to 0.39 ± 0.02 L/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 AUC 0– t (from 7483.08 ± 528.78 to 7201.24 ± 292.76 mg/L × h) ( P > 0.05) and CL (from 0.36 ± 0.02 to 0.36 ± 0.01 L/h/kg) ( P > 0.05). Conclusions The results will contribute to better use of licorice in the adjunctive therapy and provide information to study the interaction between herbs and chemotherapy.