DA-9805 is a botanical anti-Parkinsonâ??s drug candidate formulated from ethanol extracts\nof the root of Bupleurum falcatum, the root cortex of Paeonia suffruticosa, and the root of Angelica\ndahurica. The pharmacokinetics (PKs) and brain distribution of active/representative ingredients\nof DA-9805, Saikosaponin a (SSa; 1.1â??4.6 mg/kg), Paeonol (PA; 14.8â??59.2 mg/kg), and Imperatorin\n(IMP; 1.4â??11.5 mg/kg) were evaluated following the intravenous or oral administration of each\npure component and the equivalent dose of DA-9805 in rats. All three components had greater\ndose-normalized areas under the plasma concentration-time curve (AUC) and slower clearance with\nhigher doses, following intravenous administration. By contrast, dose-proportional AUC values of\nSSa, PA, and IMP were observed following the oral administration of each pure component (with\nthe exception of IMP at the highest dose) or DA-9805. Compared to oral administration of each\npure compound, DA-9805 administration showed an increase in the AUC of SSa (by 96.1â??163%) and\nPA (by 155â??164%), possibly due to inhibition of their metabolism by IMP or other component(s) in\nDA-9805. A delay in the absorption of PA and IMP was observed when they were administered as\nDA-9805. All three components of DA-9805 showed greater binding values in brain homogenates\nthan in plasma, possibly explaining why the brain-to-plasma ratios were greater than unity following\nmultiple oral administrations of DA-9805. By contrast, their levels in cerebrospinal fluid were\nnegligible. Our results further our understanding of the comprehensive PK characteristics of SSa, PA,\nand IMP in rats and the comparative PKs between each pure component and DA-9805.
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