Effects of psoralen on the pharmacokinetics of anastrozole in rats

Psoralen and anastrozole are always used together for breast cancer patients in Chinese clinics.This study investigates the effects of psoralen on the pharmacokinetics of anastrozole in rats and its potential mechanism.The pharmacokinetics of orally administered anastrozole (0.5 mg/kg) with (test group) or without (Control group) psoralen pretreatment (20 mg/kg/day for 10 days) in male Sprague-Dawley rats (six rats in each group) were investigated. The plasma concentration of anastrozole was determined using a sensitive and reliable LC-MS/MS method. Additionally, the effects of psoralen on the intestine transport and metabolic stability of anastrozole (1 μM) were investigated using a Caco-2 cell transwell model and rat liver microsome incubation systems.The results indicated that psoralen could significantly increase the Cmax (from 56.74 ± 3.17 ng/mL to 83.26 ± 6.87 ng/mL), and t1/2 (from 10.80 ± 1.05 to 14.29 ± 1.38 h) of anastrozole (p < 0.05). Psoralen could also significantly decrease the efflux ratio of anastrozole from 1.88 to 1.32 (p < 0.05). Additionally, the intrinsic clearance rates of anastrozole decreased significantly (from 62.83 to 43.97 μL/min/mg protein) (p < 0.05) with psoralen pretreatment in rat liver microsome incubation systems.This study indicates that when the rats were pretreated with psoralen, the system exposure of anastrozole would be increased significantly. The results showed that the herb-drug interaction between psoralen and anastrozole might occur when they were co-administered, and future studies in humans also need to investigate its herb-drug interaction potential.