Pharmacokinetic drug interactions involving Ginkgo biloba

Abstract

Ginkgo biloba leaf extracts (GLEs) are popular herbal remedies for the treatment of Alzheimer’s dementia, tinnitus, vertigo and peripheral arterial disease. As GLEs are taken regularly by older people who are likely to also use multiple other drugs for the treatment of, e.g. hypertension, diabetes, rheumatism or heart failure, potential herb–drug interactions are of interest. Preclinical studies of high doses/concentrations of GLEs of varying quality and standardization hinted at both an inhibition and induction of metabolic enzymes and transporters. However, in humans, positive in vitro-findings could not be replicated in vivo. At maximum recommended doses of 240 mg/day, a clinically relevant interaction potential of the standardized GLE EGb 761 could not be shown. GLE doses higher than the recommended ones led to a weak induction of the CYP2C19-mediated omeprazole 5-hydroxylation, and a weak inhibition of the CYP3A4-mediated midazolam 1′-hydroxylation, respectively. Also, the regular intake of a poorly characterized GLE at a dose of 360 mg/day slightly increased the bioavailability of talinolol, a substrate of P-glycoprotein and various organic anion-transporting polypeptides. Thus, regarding pharmacokinetic herb–drug interactions, the intake of the standardized GLE, EGb 761, together with synthetic drugs appears to be safe as long as daily doses up to 240 mg are consumed. If this applies to other extracts prepared according to the European Pharmacopoeia remains uncertain. Also, a relevant potential for drug interactions cannot be excluded for poorly standardized GLEs used in many food supplements.

• Bioavailability
• cytochrome P450 enzymes
• EGb 761
• flavonol glycosides
• Ginkgo biloba
• ginkgolic acids
• herbal extracts
• organic anion-transporting polypeptides
• P-glycoprotein
• terpene lactones

Notes

¹EGb 761®, manufacturer Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, is the active substance of the product Tebonin®. EGb 761® is a Dr. Willmar Schwabe GmbH & Co. KG registered trademark.