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INTERACTION AMITRIPTYLINE WITH KETOCONAZOLE AND QUINIDINE

INTERACTION AMITRIPTYLINE WITH KETOCONAZOLE AND QUINIDINE
阿米替林与酮康唑和奎尼丁的相互作用
批准号：
6114448
负责人：
DAVID J GREENBLATT
金额：
$4.27万
依托单位：
TUFTS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
项目状态：
已结题
起止时间：
1998-12-01 至 1999-11-30
来源：
https://reporter.nih.gov/project-details/6114448
关键词：
amitriptyline clearance rate clinical research cytochrome P450 drug interactions enzyme activity enzyme inhibitors human subject ketoconazole quinidine

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英文摘要
In vitro studies demonstrate that N-demethylation of amitriptyline to nortripty-line is mediated mainly by cytochrome P450-3A4, while hydroxylation of amitripty line to 10-hydroxy-amitriptyline is mediated in part by P450-2D6. This data pre-dicts the possibility of impaired clearance of amitriptyline in vivo by coadmin-istration of ketoconazole or quinidine, highly active and relatively specific competitive inhibitors of 3A4 and 2D6, respectively. This hypothesis will be tested in two prospective double-blind controlled kinetic-dynamic studies.
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