β‐Glucuronidase‐ and OATP2B1‐mediated drug interaction of scutellarin in Dengzhan Xixin Injection: A formulation aspect

Abstract

Scutellarin is the major and active constituent of Dengzhan Xixin Injection (DZXX), a traditional Chinese medicine prepared from the aqueous extract of Erigeron breviscapus and widely used for the treatment of various cerebrovascular diseases in clinic. In present study, the possible pharmacokinetic differences of scutellarin after intravenous administration of scutellarin alone or DZXX were explored. Additional, the potential roles of β‐glucuronidase (GLU) and OATP2B1 in drug–drug interaction (DDI) between scutellarin and constituents of DZXX were further evaluated in vitro. The plasma concentration, urinary and biliary excretion of scutellarin in rats after administration of DZXX, were significantly higher than those received scutellarin, while pharmacokinetic profile of Apigenin 7‐O‐glucuronide (AG) in rats was similar no matter AG or DZXX group. Furthermore, higher concentration in brain and plasma, however, lower level of scutellarin in intestine were observed after intravenous administration of DZXX. Finally, AG and caffeoylquinic acid esters were found to significantly inhibit GLU and OATP2B1 in vitro, which might explain, at least in part, the pharmacokinetic DDI between scutellarin and other chemical constituents in DZXX. The findings provided deep insight into the prescription‐formulating principle in DZXX for treating the cerebrovascular diseases.

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“…DZXX was approved by the State Drug Administration in 2001. Pharmacological studies indicated that breviscapin in DZXX could reduce platelet damage, improve in vivo activity and exert neuroprotective effect (Li et al, 2017a;Shi et al, 2020). The scutellarin in DZXX have anti-inflammatory effects by blocking the expression of inflammatory genes (e.g., TNF-α, IL-6, NF-κB) (Lin et al, 2019) and inhibiting the TLR4/ NF-κB signaling pathway (Zhang et al, 2017).…”