Document Detail


Studies on interactions between functional foods or dietary supplements and medicines. I. Effects of Ginkgo biloba leaf extract on the pharmacokinetics of diltiazem in rats.
MedLine Citation:
PMID:  12951478     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of Ginkgo biloba leaf extract (GBE), one of the most widely used herbal dietary supplements in Japan, on the pharmacokinetics of diltiazem (DTZ), a typical probe of cytochrome P450 (CYP) 3A, were examined in rats. The simultaneous addition of GBE to small intestine and liver microsomes inhibited the formation of N-demethyl DTZ (MA), an active metabolite of DTZ produced by CYP3A, in a concentration-dependent manner, with an IC(50) of about 50 and 182 microg/ml, respectively. This inhibition appeared to be caused, at least in part, by a mechanism-based inhibition. Both the rate of formation of MA and total amount of CYP in intestinal or hepatic microsomes after a single oral pretreatment with GBE (20 mg/kg) decreased transiently. The pretreatment significantly decreased the terminal elimination rate constant and increased the mean residence time, after intravenous administration of DTZ (3 mg/kg). Furthermore, it significantly increased the area under the concentration-time curve and absolute bioavailability after oral administration of DTZ (30 mg/kg). These results indicated that the concomitant use of GBE in rats increased the bioavailability of DTZ by inhibiting both intestinal and hepatic metabolism, at least in part, via a mechanism-based inhibition for CYP3A.
Authors:
Noriaki Ohnishi; Mayako Kusuhara; Mutsunobu Yoshioka; Kazuo Kuroda; Akihiro Soga; Fumi Nishikawa; Tomokazu Koishi; Masato Nakagawa; Satoshi Hori; Tsuyoshi Matsumoto; Masayuki Yamashita; Shunsaku Ohta; Koji Takara; Teruyoshi Yokoyama
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  26     ISSN:  0918-6158     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-02     Completed Date:  2004-04-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  1315-20     Citation Subset:  IM    
Affiliation:
Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto, Japan. ohnishi@mb.kyoto-phu.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Area Under Curve
Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors
Calcium Channel Blockers / administration & dosage,  pharmacokinetics*
Cytochrome P-450 CYP3A
Cytochromes b5 / metabolism
Diltiazem / administration & dosage,  pharmacokinetics*
Drug Interactions
Enzyme Inhibitors / pharmacology
Ginkgo biloba / chemistry*
Half-Life
Injections, Intravenous
Intestine, Small / drug effects,  enzymology,  metabolism
Male
Methylation
Microsomes / drug effects,  enzymology,  metabolism
Microsomes, Liver / drug effects,  enzymology,  metabolism
Oxidoreductases, N-Demethylating / antagonists & inhibitors
Plant Extracts / pharmacology
Rats
Rats, Wistar
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Enzyme Inhibitors; 0/Plant Extracts; 42399-41-7/Diltiazem; 9035-39-6/Cytochromes b5; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/Cytochrome P-450 CYP3A; EC 1.5.-/Oxidoreductases, N-Demethylating

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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