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.

Intestinal absorption and bioavailability of traditional Chinese medicines: a review of recent experimental progress and implication for quality control

“…For example, it was found that the absorption of baicalein, wogonin and oroxylin A were higher in Scutellaria baicalensis extract than when administrated individually. [69] Similar results were observed for cryptotanshinone and tanshinone IIA coexisting in Salvia miltiorrhiza Bge. [70] The same compound in different herbs may have different bioavailability due to the complexity of the constituents of herbal medicines, such as paeonol, whose bioavailability in Paenia suffruticosa Andr.…”

“…According to the latest reports, studies on the interactions among components in a single herb or different herbal medicines have been summarized in Table 2 [66][67][68][69][70][71][72][73][74][75][76][77][78] , within TCM preparations that have been summarized in Table 3 [78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93] .…”

Quantitative Evaluation of the Compatibility Effects of Huangqin Decoction on the Treatment of Irinotecan-Induced Gastrointestinal Toxicity Using Untargeted Metabolomics

“…And so, we think it’s reasonable to speculate that S. baicalensis and its active component BB (BB) have ameliorative effect on CPT-11-induced gastrointestinal toxicity. Because baicalin is absorbed as the form of baicalein and they have “enterohepatic circulation” phenomenon in vivo (Li et al, 2012), rats in group T/BB were administrated the mixture of BB. Mean metabolic position had been used in PCA trajectory plots to map the metabolic changes in chemicals exposure by Nicholson et al (2002).…”

Herb–drug interactions between Scutellariae Radix and mefenamic acid: Simultaneous investigation of pharmacokinetics, anti-inflammatory effect and gastric damage in rats

“…Therapeutically, they are both indicated for inflammatory diseases, with inhibition on cyclooxygenase-2 (COX-2) being one of their major antiinflammatory mechanisms (Lin and Shieh, 1996;Vane, 1971). Pharmacokinetically, they share similar metabolic pathways: the bioactive components of SR and the majority of the NSAIDs are reported to undergo extensive hepatic Phase II metabolisms (Kiang et al, 2005;Li et al, 2012). These similarities may increase the opportunity of co-administration by patients and, at the same time, the potential of pharmacokinetic and/or pharmacodynamic interactions.…”