title: Effects of continuous ingestion of green tea or grape seed extracts on the pharmacokinetics of midazolam.
abstract: Limited systematic data on herb-drug interaction are available, despite many opportunities to concomitant use of herb with prescribed drugs. We investigated the effects of 15 herbal extracts in dietary supplements on CYP2C9, CYP2D6 and CYP3A4 activities in human liver microsomes. Strong inhibition of these CYP activities was found by the addition of green tea extracts (GTE) or grape seed extracts (GSE) in vitro. To examine the effects of these extracts on CYP3A activities in vivo, the pharmacokinetics of midazolam (MDZ) was analyzed in rats. Although single treatments with these extracts had negligible effects, 1 week of treatment with them resulted in a significant increase in the ke of intravenously administered MDZ, indicating the induction of CYP3A in the liver. In contrast, 1 week of treatment with GTE, but not GSE, caused a significant increase in the C(max) and AUC(0-infinity) of orally administered MDZ without change in the t(1/2), suggesting a reduction in CYP3A activity in the small intestines. These studies indicate that subchronic ingestion of GTE or GSE may alter the pharmacokinetics of MDZ, and the effects of GTE on CYP3A activity appear opposite between liver and small intestine, which could not be predicted from in vitro experiments.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Noritaka
authors.initials: N
authors.lastname: Ariyoshi
authors.forename: Akira
authors.initials: A
authors.lastname: Kotani
authors.forename: Itsuko
authors.initials: I
authors.lastname: Ishii
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakasa
authors.forename: Mayuri
authors.initials: M
authors.lastname: Ida
authors.forename: Hideo
authors.initials: H
authors.lastname: Nakamura
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Kimura
authors.forename: Maharu
authors.initials: M
authors.lastname: Kimura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Kusu
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohmori
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Nakazawa
authors.forename: Mitsukazu
authors.initials: M
authors.lastname: Kitada
mesh_terms: D000328:Adult; D000818:Animals; D028241:Camellia sinensis; D004327:Drinking Behavior / Q000502:physiology; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012639:Seeds; D013662:Tea; D027843:Vitis
chemical_list: D004365:Drugs, Chinese Herbal; D013662:Tea; D008874:Midazolam