| In Vivo Inhibition of CYP3A-Mediated Midazolam Metabolism by Anchusan in Rats. | |
| | |
MedLine Citation:
|
PMID: 21358120 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Cytochrome P450 (CYP)-mediated drug interactions caused by Kampo medicine have not been investigated sufficiently. The current study was conducted to reveal the effect of anchusan, a commonly used Kampo formula for gastrointestinal disease, on CYP3A-mediated drug metabolism in rats. The pharmacokinetics of midazolam (MDZ) was investigated after the single or one-week administration of anchusan (500 mg/kg) to evaluate its inhibitory and inducible effect on CYP3A, respectively. MDZ was administrated 16 h after the last anchsan treatment in the multiple dose study, while their intervals were 2 or 16 h in the single dose study. Unexpectedly, the multiple-pretreatment of anchusan increased the AUC of MDZ by 2.4-fold rather than decreasing it, and the CYP3A contents and activities were unchanged in hepatic and intestinal microsomes of these rats. In contrast, no significant inhibitory effects on MDZ metabolism were observed by the single anchusan pretreatment. In vitro study showed that the preincubation of anchusan and some of its component extracts with rat liver microsomes reduced CYP3A activity in a time- and NADPH-dependent manner. These results suggested that anchusan increased the serum MDZ concentration in rats, at least in part, by the time-dependent inhibition of CYP3A. |
| | |
Authors:
|
Yusuke Saito; Yuki Nishimura; Norimitsu Kurata; Mariko Iwase; Kayo Aoki; Hajime Yasuhara |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-2-24 |
Journal Detail:
|
Title: Journal of pharmacological sciences Volume: - ISSN: 1347-8648 ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
|
Created Date: 2011-3-1 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101167001 Medline TA: J Pharmacol Sci Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of Pharmacology, School of Medicine, Showa University, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Mechanism of the Cardioprotective Effects of Docetaxel Pre-administration Against Adriamycin-Induced...
Next Document: Glutathione Biosynthesis via Activation of the Nuclear Factor E2-Related Factor 2 (Nrf2) - Antioxida...