SALT LAKE CITY, Utah—An ingredient in licorice—widely used in foods and herbal medicines—blocks cyclosporine absorption, significantly reducing the drug's serum levels and duration, researchers from Taiwan reported today at the American Chemical Society's 237th National Meeting.1
"The bioavailability of cyclosporine was greatly reduced."—Pei-Dawn Lee Chao, PhD
Senior investigator Pei-Dawn Lee Chao, PhD, who presented the report at the ACS meeting, had previously reported that licorice also alters methotrexate pharmacokinetics.2 The researchers are in the Department of Pharmacy at China Medical University in Taiwan. This is the first report of an interaction between licorice and cyclosporine, which is widely used in a number of rheumatoid conditions.

Licorice inhibits CYP3A4

"Licorice and its major constituent glycyrrhizin (GZ) have been reported to inhibit cytochrome-dependent metabolic enzymes and P-glycoprotein (Pgp), an efflux transporter. Cyclosporine, an important immunosupressant with a narrow therapeutic window, is a substrate of CYP3A4 and Pgp. This study investigated the effects of licorice and GZ on the absorption and disposition of cyclosporine," Dr. Chao said.

The investigators gave rats oral doses of cyclosporine with and without various dosage regimen of GZ and licorice decoction (LD). They then analyzed blood concentration of cyclosporine by fluorescence polarization immunoassay.

"Unexpectedly, the Cmax and AUC0-t of cyclosporine were significantly decreased by co-administration with GZ and LD, indicating that the bioavailability of cyclosporine was greatly reduced," Dr. Chao said. Licorice had the opposite effect on methotrexate levels.

Interaction might affect therapeutic efficacy

The researchers note that this interaction is likely to be especially important in transplant patients, where the concurrent use of licorice with cyclosporine might reduce cyclosporine serum below those needed to suppress transplant rejection.

References
1. Chao PDL. Glycyrrhizin and licorice significantly affect the pharmacokinetics of cyclosporine in rats. Presented at: American Chemical Society 237th National Meeting, Salt Lake City, March 24, 2009. Presentation no. AGFD 081.
2. Lin SP, Tsai SY, Hou YC, Chao PD. Glycyrrhizin and licorice significantly affect the pharmacokinetics of methotrexate in rats. J Agric Food Chem. 2009 Feb 11. [Epub ahead of print]