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  • Title: Plasma levels and distribution of flavonoids in rat brain after single and repeated doses of standardized Ginkgo biloba extract EGb 761®.
    Author: Rangel-Ordóñez L, Nöldner M, Schubert-Zsilavecz M, Wurglics M.
    Journal: Planta Med; 2010 Oct; 76(15):1683-90. PubMed ID: 20486074.
    Abstract:
    It is undisputed that terpene lactones and flavonoid glycosides of Ginkgo biloba are responsible for most of the extracts (e.g., EGb 761®) pharmacological actions. This investigation focused on the pharmacokinetic and the ability of the flavonoid constituents to cross the blood-brain barrier in rats, after single (600 mg/kg) or repeated (8 days, 100, or 600 mg/kg) oral administration of EGb 761®, and their distribution in different areas of the brain. For this purpose, we developed an HPLC-fluorescence method for the determination of the Ginkgo flavonoid metabolites (quercetin, kaempferol, and isorhamnetin derivatives) in the brain and plasma. A single dose of 600 mg/kg EGb 761® resulted in maximum plasma concentrations of 176, 341, and 183 ng/mL for quercetin, kaempferol, and isorhamnetin/tamarixetin, respectively and in maximum brain concentrations of 291 ng/g protein for kaempferol and 161 ng/g protein for isorhamnetin/tamarixetin. In comparison, the repeated administration of the same dose for 8 days led to an approximate 4.5-fold increase in the plasma concentration for quercetin, 11.5-fold increase for kaempferol, and 10-fold increase for isorhamnetin/tamarixetin. In the brain, an approximate 2-fold increase was observed for kaempferol and isorhamnetin/tamarixetin. About 90% of the determined flavonoids were distributed in the hippocampus, frontal cortex, striatum, and cerebellum, which together represent only 38% of the whole brain.
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