Pretreatment with Ginkgo biloba extract weakens the hypnosis action of phenobarbital and its plasma concentration in rats.
In a previous study, we found that orally administered Ginkgo biloba extract (GBE) induced hepatic cytochrome P450 (CYP) in rats, especially the CYP2B type. This fact suggested that GBE influenced the availability and safety of drugs that were metabolized via CYP2B type enzymes. To confirm this possibility, in this study we examined the effect of feeding a 0.1, 0.5 and 1.0% GBE diet for 2 weeks on the pharmacokinetics and pharmacological action of phenobarbital, which is known to be metabolized by CYP2B in Wistar rats. The feeding of GBE markedly shortened the sleeping time in rats. Furthermore, the maximal phenobarbital plasma concentration (Cmax) and the 24-h area under the curve (AUC0-24) were decreased in rats fed GBE. These findings indicate that GBE reduces the therapeutic potency of phenobarbital via enhancement of cytochrome P450 expression, and raises the possibility that GBE and drug interactions may occur clinically.
Kubota
Yoko
Y
Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan.
Kobayashi
Kyoko
K
Tanaka
Naoko
N
Nakamura
Kazuki
K
Kunitomo
Masaru
M
Umegaki
Keizo
K
Shinozuka
Kazumasa
K
D000284:Administration, Oral; D000818:Animals; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis / Q000097:blood; D004334:Drug Administration Schedule; D020441:Ginkgo biloba / Q000737:chemistry*; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D010634:Phenobarbital / Q000037:antagonists & inhibitors* / Q000097:blood* / Q000494:pharmacology*; D010936:Plant Extracts / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects; D013997:Time Factors
D010936:Plant Extracts; D019362:Cytochrome P-450 CYP2B1; D010634:Phenobarbital