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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：
6304523
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：
1999
资助国家：
美国
项目状态：
已结题
起止时间：
1999-12-01 至 2001-02-28
来源：
https://reporter.nih.gov/project-details/6304523
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 nortriptyline is mediated mainly by cytochrome P450-3A4, while hydroxylation of amitriptyline to 10-hydroxy-amitriptyline is mediated in part by P450-2D6. These data predict the possibility of impaired clearance of amitriptyline in vivo by coadministration 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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