Pharmacokinetic interactions among major bioactive components in Radix Scutellariae via metabolic competition

ABSTRACT Baicalein (B), wogonin (W) and oroxylin A (OA) are major components in Radix Scutellariae with similar pharmacokinetic properties. Due to the co‐presence of these three flavones in herbal formulations for Radix Scutellariae , they are likely consumed together. The aim of this study is to investigate whether the pharmacokinetics of individual flavones is influenced by each other and the underlying mechanism of the interaction. Various systems were utilized in the current study including a rat in vivo study, a Caco‐2 cell monolayer model and a rat in situ single‐pass intestinal perfusion as well as in vitro enzymatic kinetics studies. The B, W and OA given singly as well as in a mixture were administered and the corresponding pharmacokinetic parameters were calculated and compared. After co‐administration of the three flavones to rats, OA absorption increased significantly in comparison with when OA was administered alone. Mechanistic studies on the Caco‐2 cell monolayer and rat in situ single‐pass intestinal perfusion models revealed that co‐administration of B, W and OA could significantly enhance their absorption and decrease the extent of phase II metabolism. Further in vitro enzymatic study and a transport study in transfected MDCK cells revealed that metabolic competition rather than membrane transporters might contribute to the pharmacokinetic interactions. The co‐presence of multiple active components would result in metabolic interactions, which may induce further changes in pharmacodynamics. Copyright © 2012 John Wiley & Sons, Ltd.