Pharmacokinetics of geniposide in Zhi-Zi-Hou-Pu decoction and in different combinations of its constituent herbs.

Zhi-Zi-Hou-Pu decoction (ZZHPD), a classic antidepressant formula, is composed of Gardenia jasminoides Ellis (ZZ), Fructus aurantii immaturus (ZS) and Cortex magnoliae officinalis (HP). ZZHPD has attracted a great deal of attention for its antidepressant effects. The aim of this study was to compare the pharmacokinetics of geniposide (one of the predominant active ingredients) after oral administration of different combinations of ZZHPD and to explore the influence of herb-herb interaction on the pharmacokinetics of geniposide. Twenty four rats were divided randomly into four groups and were administered one of the four extracts: ZZ, ZZ-HP, ZZ-ZS and ZZHPD (ZZ-HP-ZS) via intragastric gavage with approximately the same dose of 40.65 mg/kg geniposide (an effective human daily dose of ZZHPD). Plasma concentrations of geniposide were determined using an HPLC method. Pharmacokinetic parameters were calculated from the plasma concentration-time data. Compared with ZZ alone, the ZZ-ZS combination delayed T(max) and ZZ-HP, ZZ-ZS, ZZHPD remarkably shortened the T(1/2) of geniposide. In addition, ZZ-HP, ZZ-ZS, ZZHPD obviously increased the AUC of geniposide. The result illustrated that the oral bioavailability of geniposide was dramatically enhanced when ZZ was combined with HP or/and ZS. It can be deduced that herb-herb interaction may increase the absorption, and significantly improve the oral bioavailability of geniposide in rats.