Effects of Ginkgo biloba extract on pharmacokinetics and pharmacodynamics of tolbutamide and midazolam in healthy volunteers.
This study was undertaken to clarify the influence of repeated oral administration of Ginkgo biloba extract (GBE) on CYP2C9 and CYP3A4. CYP2C9 probe (tolbutamide, 125 mg) and CYP3A4 probe (midazolam, 8 mg) were orally administered to 10 male healthy volunteers before and after GBE intake (360 mg/d) for 28 days, and they received 75 g glucose after the dosing of tolbutamide. Plasma drug concentrations and blood glucose levels were measured. The area under concentration versus time curve (AUC0-infinity) for tolbutamide after GBE intake was slightly but significantly (16%) lower than that before GBE intake. Concomitantly, GBE tended to attenuate AUC0-2 of blood glucose-lowering effect of tolbutamide. AUC0-infinity for midazolam was significantly (25%) increased by GBE intake and oral clearance was significantly (26%) decreased. Thus, it is suggested that the combination of GBE and drugs should be cautious in terms of the potential interactions, especially in elderly patients or patients treated with drugs exerting relatively narrow therapeutic windows.
Uchida
Shinya
S
Department of Pharmacokinetics, Center of Excellence Program in the 21st Century, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Yamada
Hiroshi
H
Li
Xiao Dong
XD
Maruyama
Shuji
S
Ohmori
Yuki
Y
Oki
Tomomi
T
Watanabe
Hiroshi
H
Umegaki
Keizo
K
Ohashi
Kyoichi
K
Yamada
Shizuo
S
D000328:Adult; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics; D019540:Area Under Curve; D004347:Drug Interactions; D020441:Ginkgo biloba / Q000737:chemistry*; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics; D008297:Male; D008874:Midazolam / Q000493:pharmacokinetics*; D010936:Plant Extracts / Q000494:pharmacology*; D014044:Tolbutamide / Q000493:pharmacokinetics*
D014151:Anti-Anxiety Agents; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D014044:Tolbutamide; D008874:Midazolam