Biol. Pharm. Bull. 28(10) 1897—1902 (2005)

herb–drug interactions are recognized as a clinically important problem. Recently, various clinical and non-clinical studies including in vitro studies related to pharmacokinetic interactions between herbs and new drugs have been reported. Durr et al. reported that the administration of St. John’s Wort (Hypericum perforatum) extract to 8 healthy male volunteers during 14 d resulted in an 18% decrease of digoxin exposure after a single digoxin dose (0.5 mg), in 1.4and 1.5-fold increased expressions of duodenal P-glycoprotein/MDR1 and CYP3A4, respectively, and in a 1.4-fold increase in the functional activity of hepatic CYP3A4 in clinical study. However, to our knowledge, there has been no report dealing with the pharmacokinetic interactions between two herbs. In the course of our clinical studies of Kampo medicine, we observed changes in various pharmacokinetic parameters of a marker component of Kampo medicine. In this article, we demonstrate a pharmacokinetic interaction between two herbs by various non-clinical investigations of a representative marker component of a herb. Glycyrrhizinic acid (GL), one of the main components of licorice root (Glycyrrhizae radix), shows various biological activities such as having an anti-inflammatory and an antihepatitis effect and is contained in many types of Kampo medicines. GL is a glycoside having two glucuronic acid molecules attached to the hydroxyl group at C-3 position of glycyrrhetic acid (GA) (Fig. 1). Since GA is derived from GL via metabolism as mentioned below, GA has been frequently used as a pharmacokinetic marker of Kampo medicines including licorice. Kampo medicines are orally administered so that the chemical components contained in the Kampo medicines may be manipulated by the intestinal flora before being absorbed into the body. For example, the following hydrolysis, glycosides are transformed by intestinal flora to the corresponding aglycones. In a previous paper, we reported that only GA was detected instead of GL in the plasma when GL was orally administered to rats. In addition, we clarified that GA was not detected in the plasma after oral administration of GL to germ-free rats having no intestinal bacteria. These results suggest that GL is hydrolyzed to GA by intestinal bacteria after oral administration of GL to rats, and is absorbed as GA from the intestinal tract. Absorption of GL might be smaller October 2005 Biol. Pharm. Bull. 28(10) 1897—1902 (2005) 1897