Plasma and Brain Levels of Terpene Trilactones in Rats after an Oral Single Dose of StandardizedGinkgo bilobaExtract EGb 761®

Abstract

Several studies indicate that the terpene trilactones (TTL) of EGb 761® are responsible for most of its pharmacological action in the brain . Therefore, we investigated the ability of the TTL to cross the blood brain barrier in rats after a single oral administration (600 mg/kg) of EGb 761® and compared it with the plasma levels. In addition, we checked the pharmacokinetic characteristics of an application of EGb 761® against a similar amount of pure substances. For this purpose, we developed a sensitive HPLC-(APCI)-MS method for the determination of the Ginkgo biloba TTL (ginkgolide A [GA], B [GB], C [GC] and bilobalide [Bb]) in plasma as well as in brain tissue. The following animal study shows that the oral application of 600 mg/kg EGb 761® results in significant GA, GB, and Bb concentrations in plasma as well as in the CNS of the rodents, while the GC concentration was below the detection limit of the analytical method in both matrices. GA, GB, and Bb brain concentrations showed a rapid increase up to 55 ng/g, 40 ng/g, and 98 ng/g with no difference of the characteristic after extract or pure substance application. Regarding the plasma levels, significant higher C(max) and AUC values were detected after application of the extract EGb 761®. These results allow for the first time a discussion of pharmacological effects with the knowledge of the pharmacokinetic behavior of the TTL in target tissues.

Ginkgo Extract EGb761 Confers Neuroprotection by Reduction of Glutamate Release in Ischemic Brain

“…Both classes of compounds occur prominently in Ginkgo extracts, and they reach micromolar concentrations after intake of Ginkgo extract EGb761 in human and experimental studies [29]. Moreover, both classes of compounds have recently been shown to cross the blood-brain barrier in significant amounts [30,31]. However, bilobalide may be the most active constituent of the extract.…”

Interactions of pharmacokinetic profile of different parts from Ginkgo biloba extract in rats

“…Several methods and strategies have been established for pharmacokinetic studies of terpene lactones and flavonoids contained in GBE. (Mauri et al, 2006;Mauri et al, 2003;Rangel-Ordonez et al, 2010;Ude et al, 2011;Wang et al, 2003;Xie et al, 2008;Zhao et al, 2007). However, there are few reports on the pharmacokinetic properties of simultaneous determination of flavonoid aglycones, flavonoid glycosides and terpene lactones.…”

Brain permeability of bilobalide as probed by microdialysis before and after middle cerebral artery occlusion in mice

“…120 mg EGb 761) yielded bilobalide plasma levels of 0.05-0.15 µM [13][14][15][16]. In rats, oral administration of Ginkgo extracts and/or pure bilobalide caused dosedependent increases of bilobalide plasma levels from 0.5 to 7.5 µM [13,17,18]. Little information, however, is available on concentrations of Ginkgo constituents in the brain.…”