Pharmacokinetics of Isoliquiritigenin and Its Metabolites in Rats: Low Bioavailability Is Primarily Due to the Hepatic and Intestinal Metabolism

Abstract

Isoliquiritigenin, a chalcone found in licorice has shown a variety of biological activities including antioxidative, anti-inflammatory, estrogenic, chemopreventive and antitumor effects. Thus, pharmacokinetics of isoliquiritigenin and its metabolites [liquiritigenin, glucuronidated isoliquiritigenin (M1), and glucuronidated liquiritigenin (M2)] after intravenous and oral administration of isoliquiritigenin was evaluated in rats. The pharmacokinetics of isoliquiritigenin, liquiritigenin, M1, and M2 showed no dose dependence after both intravenous and oral administration of isoliquiritigenin. Although approximately 92.0% of the oral isoliquiritigenin was absorbed, the extent of the absolute bioavailability value was only 11.8% of the oral dose. The low absolute bioavailability value of isoliquiritigenin might be due to the considerable metabolism of isoliquiritigenin in the small intestine and liver. This was supported by the facts that the ratios of AUC(M1)/AUC(isoLQ) and AUC(M2)/AUC(isoLQ) were high (over 0.25), isoliquiritigenin disappeared, and M1 and M2 were formed mainly in S9 fractions of the liver and small intestine. The affinities of liquiritigenin, isoliquiritigenin, M1, and M2 were high in the liver, small intestine, large intestine, and/or kidney.