Background: Polyethylene glycol 400 (PEG400), as a good traditional Chinese medicine
solvent, diluent and solubilizer, is widely used as a main pharmaceutical excipient in traditional Chinese
medicine compound preparations containing active ingredient baicalin. PEG400 could increase
the solubility and release of baicalin in vivo, but it was unknown that PEG400 affected the absorption
and distribution of baicalin or not.
Objective: At present, the effects of PEG400 on the pharmacokinetic characteristics and tissue distribution
behaviors of the main flavonoid metabolites baicalin, baicalein 6-O-β-D-glucopyranoside (B6G)
and baicalein after oral administration of baicalin were investigated by a rapid, efficient and sensitive ultra-
high performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method.
Moreover, we respectively studied the effects of PEG400 on the activities and protein expressions of two
subtypes UDP-glucuronyltransferase 1 A8/A9 (UGT1A8 and UGT1A9) of UDP-glucuronosyltransferases
(UGTs) in vitro and in vivo experiments to determine the partial mechanisms by which PEG400 altered
the pharmacokinetics and tissue distribution behaviors of the three flavonoid metabolites.
Methods: A rapid, efficient and sensitive ultra-high performance liquid chromatography with tandem
mass spectrometry (UPLC-MS/MS) method and ELISA and so on.
Results: The results showed that PEG400 significantly increased the Cmax and AUC0-t values
(P < 0.05 or P < 0.01) of baicalin and B6G while baicalein could not be quantified due to its extremely
low concentration (lower the LLOQ) in plasma. Baicalin, B6G and baicalein were mainly distributed in
the stomach, small intestine, kidney and liver. PEG400 changed the distribution of three flavonoid metabolites
in various tissues and also increased the activities and expressions of UGT1A8 and UGT1A9.
Conclusion: In conclusion, PEG400 significantly altered the pharmacokinetic characteristics and tissue distribution
behaviors of three flavonoid metabolites may partly result from PEG400 upregulated the activities
and expressions of the drug biphasic metabolic enzymes UGT1A8 and UGT1A9, which provided a material
basis and useful information to reveal the mechanism of action and clinical application of PEG400.