Glycyrrhizin and licorice significantly affect the pharmacokinetics of methotrexate in rats

Abstract

Glycyrrhizin (GZ) and licorice (root of Glycyrrhiza uralensis) are worldwide food additives and important oriental phytomedicines. This study investigated the biological fate of GZ by orally giving GZ and licorice decoction (LD) to rats. The serum concentrations of GZ and glycyrrhetic acid (GA) were determined by high performance liquid chromatography. The results showed that GZ was not detected and GA was present in serum until 3 days postdosing of GZ and LD. To evaluate the effects of GZ and licorice on the pharmacokinetics of methotrexate (MTX), an important immunosuppressant with a narrow therapeutic window, rats were orally given MTX with and without GZ and LD in different dosage regimens. The serum MTX concentration was determined by fluorescence polarization immunoassay. The results revealed that the AUC and MRT of MTX were significantly increased by GZ and LD. In conclusion, the concurrent use of GZ or licorice with MTX should be with caution.