Plasma and Brain Levels of Terpene Trilactones in Rats after an Oral Single Dose of Standardized Ginkgo biloba Extract EGb 761®

Several studies indicate that the terpene trilactones (TTL) of EGb 761 (R) are responsible for most of its pharmacological action in the brain [1]. 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 (R) and compared it with the plasma levels. In addition, we checked the pharmacokinetic characteristics of an application of EGb 761 (R) 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 (R) 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 (R). 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.