Ginkgo metabolites

Ginkgo extract has no effect on the hepatic microsomal drug oxidation system, as measured by antipyrine elimination, even at doses of 400 mg per day (Duche et al. 1989). Ginkgo metabolites, the substituted benzoic acids (4-hydroxybenzoic acid conjugate, 4-hydroxyhippuric acid, 3-methoxy-4-hydroxyhippuric acid, 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, hippuric acid and 3-methoxy-4-hydroxybenzoic acid [vanillic acid]), are excreted in urine (Pietta et al. 1997). 

Pietta, P.G. et al.. Identification of flavonoid metabolites after oral administration to rats of a Ginkgo biloba extract, J. Chromatogr. B — Biomed. Appl, 673, 75, 1995. 

Animal studies In the study by Pietta et al. (39), a single dose of ginkgo leaf extract (EGb 761) was administered orally to rats. Metabolites found in the urine represented less than 40% of the flavonoids administered. The presence of phenylalkyl acids in the rat urine but not in the human urine (33,39) indicates that the flavonols were more extensively metabolized in humans than in rats. In the study by Watanabe et al. (40), mice received a diet containing ginkgo leaf extract (EGb761 36mg/kg daily) or a standard diet without the extract for four weeks. Afterwards, plasma levels of quercetin (12.0ng/mL vs. 4.8ng/mL), kaempferol (7.0ng/mL vs. 3.2 ng/ mL), and isorhamnetin (49.6ng/mL vs. Ong/mL) in both treatment groups were determined. The study indicates that these compounds can be absorbed intact into the blood stream. 

Liebgott, T. Miollan, M. Berchadsky, Y. Drieu, K. Culcasi, M. Pietri, S. Complementary cardioprotective effects of flavonoid metabolites and terpenoid constituents of Ginkgo biloba extract (EGb 761) during ischemia and reperfusion. Basic Res. Cardiol, 2000, 95 368-377. 

Pietta PG, Gardana C, Mauri PL. Identification of Ginkgo flavonol metabolites after oral administration to humans. J Chromatogr Biomed Sci Appl 1997 693 249-255. 

Ginkgolic acid is a mixture of several 2-hydroxy-6-alkyIbenzoic acids, two of which (alkyl = 1-octene or 3-decene) were baseline resolved on a 45 C Cjg column (A = 308nm) with a 92/7/1 acetonitrile/water/acetic acid mobile phase [1053]. Elution was complete in 6 min and peaks of interest were well resolved from all extracted material. In a separate study, Pietta et al. [1054] isolated six metabolites (hippuric acid, 4-hydroxy- and 3-methoxy-4-hydroxyhippuric acid, 4-hydroxy-, 3,4-dihydroxy-, and 3-methoxy-4-hydroxybenzoic acid) of Ginkgo biloba leaf extracts from urine and blood samples and analyzed on a Cjg column (photodiode array detector). An 88/5/5/2 water/acetonitrile/methanol/acetic acid mobile phase generated good resolution and complete elution in 15 min. The standard used was at the 1 mg/mL level. 

---