Pharmacokinetics and Relative Bioavailability of Flavonoids between Two Dosage Forms of Gegen-Qinlian-Tang in Rats

Abstract

Gegen-Qinlian-Tang (GQT), a popular Chinese medicine prescription, consists of Puerariae Radix, Scutellariae Radix, Coptidis Rhizoma, and Glycyrrhizae Radix. This study investigated the pharmacokinetics of GQT in rats and compared the bioavailability between two dosage forms, that is, traditional decoction (TD) and concentrated powder (CP). Rats were given TD and CP of GQT in a crossover design, and blood samples were withdrawn at predetermined time points. The quantitation methods of ten constituents in two dosage forms of GQT and in serum specimen using HPLC were developed and validated in this study. The pharmacokinetic parameters were calculated using noncompartment model. The results showed that daidzein, baicalein, wogonin, berberine, palmatine, and coptisine were not found in the circulation, whereas the sulfates/glucuronides of daidzein, baicalein, and wogonin were the major forms after oral administration of GQT. Comparison between two dosage forms indicated that the AUC(0-t) of daidzein sulfates/glucuronides after administration of CP was significantly lower than that of TD by 28.9%, whereas the bioavailabilities of baicalin/baicalein and wogonoside/wogonin were comparable between two dosage forms. In conclusion, the major flavonoids of GQT were extensively metabolized into sulfates/glucuronides and present as the major molecules in the circulation. TD of GQT revealed higher bioavailability of daidzin/daidzein than CP.

Figure 1

Chemical structures of major constituents in GQT.

Figure 2

HPLC chromatogram of GQT decoction. 1: puerarin, 2: daidzin, 3: coptisine, 4: baicalin, 5: daidzein, 6: palmatine, 7: berberine, 8: baicalein, 9: glycyrrhizin, 10: wogonin, IS: amyl paraben.

Figure 3

Typical HPLC chromatograms of serum specimens after administration of GQT to rat. (a) Serum specimen, (b) serum specimen after hydrolyzed with glucuronidase, (c) serum specimen after hydrolyzed with sulfatase/glucuronidase. 1: daidzein, 2: baicalein, 3: wogonin and IS: propyl paraben.

Figure 4

Mean (±S.E.) serum concentration: time profiles of the sulfates/glucuronides (S/G) and glucuronides (G) of daidzein (a), baicalein (b), and wogonin (c) after oral administration of traditional decoction (TD) and concentrated powder (CP) of GQT in six rats.