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The Effects of Ginkgo biloba Extracts on the Pharmacokinetics and Pharmacodynamics of Donepezil

From the Department of Clinical Pharmacology (Dr. Yasui-Furukori, Dr. Tateishi) and Neuropsychiatry (Dr. Yasui-Furukori, Dr. Furukori, A. Kaneda, Dr. Kaneko), Hirosaki University School of Medicine, Hirosaki, Japan, and the Department of Psychiatry, Koroishi-Akebono Hospital, Kuroishi, Japan (Dr. Furukori, A. Kaneda).

The effects of ginkgo supplementation on the steady-state plasma concentration of donepezil and the activity of cholinesterase in red blood cells and cognitive function were examined. Fourteen inpatients with Alzheimer's disease received donepezil 5 mg/day, supplemented with extracts of Ginkgo biloba 90 mg/day for 30 days. Blood samples were collected before and during ginkgo supplementation and 30 days after its discontinuation, together with an assessment of cognitive function. Plasma drug concentration was measured using high-performance liquid chromatography (HPLC), and cholinesterase in red blood cells was measured using Ellman methods. Cognitive function was evaluated using the Mini-Mental Scale Examination (MMSE). Plasma concentration of donepezil during ginkgo supplementation (mean ± SD [95% confidence interval]; 24.4 ± 12.6 ng/mL [17.1-31.7 ng/mL]) was not significantly different from that before ginkgo supplementation (22.7 ± 10.3 ng/mL [16.8-28.7 ng/mL]) or that 4 weeks after its discontinuation (25.0 ± 12.9 ng/mL [17.6-32.4 ng/mL]). There was no significant difference between cholinesterase in red blood cells before ginkgo supplementation (1.75 ± 0.21 U [1.63-1.87 U]), during ginkgo supplementation (1.91 ± 0.27 U [1.76-2.07 U]), and 4 weeks after its discontinuation (1.83 ± 0.29 U [1.66-2.00 U]). Ginkgo supplementation did not alter MMSE scores throughout the study. The present study shows that ginkgo supplementation does not have major impact on the pharmacokinetics and pharmacodynamics of donepezil.

Key Words: Donepezil • Ginkgo biloba • pharmacokinetics • pharmacodynamics • drug-herb interaction • Alzheimer's disease

Address for reprints: Norio Yasui-Furukori, MD, PhD, Department of Clinical Pharmacology, Hirosaki University, School of Medicine, Hirosaki 036-8562, Japan.

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