Glycyrrhizin and licorice significantly affect the pharmacokinetics of methotrexate in rats.
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.
Lin
Shiuan-Pey
SP
Graduate Institute of Pharmaceutical Chemistry, School of Pharmacy, China Medical University, Taichung 40402, Taiwan.
Tsai
Shang-Yuan
SY
Hou
Yu-Chi
YC
Chao
Pei-Dawn Lee
PD
D000284:Administration, Oral; D000818:Animals; D004347:Drug Interactions; D006034:Glycyrrhetinic Acid / Q000097:blood / Q000378:metabolism; D006035:Glycyrrhiza / Q000737:chemistry*; D019695:Glycyrrhizic Acid / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010936:Plant Extracts / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D010936:Plant Extracts; D019695:Glycyrrhizic Acid; D006034:Glycyrrhetinic Acid; D008727:Methotrexate