Ginkgo biloba

The exact mechanism is not known.

Human pharmacological data show increased EEG vigilance in geriatric subjects, reduction in blood viscosity and improved cerebral perfusion in specific areas in healthy men (60-70 years) and reduction in platelet aggregation. Additionally, vasodilating effects on forearm blood vessels causing increased regional blood flow are shown.

Following oral administration (as solution) of 120 mg of the Ginkgo extract, the mean absolute bioavailability has been shown in humans for the terpene lactones ginkgolide A (80%), ginkgolide B (88%) and bilobalide (79%). Peak plasma concentrations of terpene lactones were in the range of 16-22 ng/ml for ginkgolide A, 8-10 ng/ml for ginkgolide B and 27-54 ng/ml of bilobalide when given as tablets. The corresponding halflives of ginkgolide A and B and bilobalide were 3-4, 4-6 and 2-3 hours, respectively. 120 mg Ginkgo biloba extract given as solution peak plasma concentrations were 25-33 ng/ml, 9-17 ng/ml and 19-35 ng/ml for ginkgolide A, B and bilobalide, respectively. The related half-life for ginkgolide A was 5 hours, for ginkoglide B 9-11 hours and for bilobalide 3-4 hours.

Chronic toxicity

Chronic toxicity was tested orally over 6 months in rats and dogs with daily dosages of 20 and 100 mg/kg BW (corresponding to safety factor of up to 3.3 in rats and 11.6 in dogs), as well as with incremental doses of 300, 400 and 500 mg/kg BW (rat) or 300 and 400 mg/kg BW (dog) (corresponding to a safety factor of up to 16.8 in rats and 46.3 in dogs). The results showed only for dogs a low toxicity in the highest dosage group.

Reproductive toxicity

Only limited information is available on reproductive toxicity of the Ginkgo biloba dry extract. The published data are contradictory. While an older study in rats and rabbits and a newer study in mice revealed no teratogenic, embryotoxic or adverse reproductive effects, another study in mice showed effects on reproductive parameters, such as fertility and reproductive performance and it evoked vaginal bleeding. Also tests with unspecified or slightly different Ginkgo extracts pointed towards effects on fetal development (with and without maternal toxicity) or caused subcutaneous bleeding, hypopigmentation, growth inhibition and anophthalmia in chicken embryos.

Adequate tests on reproductive toxicity do not exist.

Mutagenicity, carcinogenicity

An Ames-Test on mutagenicity does not give any reason for concern. Tests on carcinogenicity are not available.

An extract similar to the monograph relevant extract was tested in a series of studies for genotoxicity and carcinogenicity. It was positive for gene mutation in bacteria. A peripheral mouse erythrocytes micronucleus test provided a negative result in male and an equivocal result in female animals.

The thyroid gland tumours found in a rat carcinogenicity study and hepatocellular carcinoma found in a mouse carcinogenicity study are considered rodent specific, non-genotoxic response associated (with long-term treatment) with high doses of hepatic enzyme inducers. These types of tumours are not considered relevant to humans. The extract did not induce measurable genotoxic effects in mice up to 2000 mg/kg.