Effect of diethyldithiocarbamate (DDC) and ticlopidine on CYP1A2 activity and caffeine metabolism: an in vitro comparative study with human cDNA-expressed CYP1A2 and liver microsomes

被引：0
作者：
Marta Kot
Władysława A. Daniel
机构：
[1] Polish Academy of Sciences,Department of Pharmacokinetics and Drug Metabolism, Institute of Pharmacology
来源：
Pharmacological Reports | 2009年 / 61卷
关键词：
cytochrome P450; cDNA-expressed CYP1A2; human liver microsomes; caffeine metabolism; DDC; ticlopidine; furafylline;
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学科分类号：
摘要：
The aim of the present study was to test the effect of diethyldithiocarbamate (DDC), which is regarded as a cytochrome P450 (CYP) CYP2A6 and CYP2E1 inhibitor, and ticlopidine, an efficient CYP2B6, CYP2C19 and CYP2D6 inhibitor, on the activity of human CYP1A2 and the metabolism of caffeine (1-N-, 3-N- and 7-N-demethylation, and C-8-hydroxylation). The experiment was carried out in vitro using human cDNA-expressed CYP1A2 (Supersomes) and human pooled liver microsomes. The effects of DDC and ticlopidine were compared to those of furafylline (a strong CYP 1A2 inhibitor). A comparative in vitro study provides clear evidence that ticlopidine and DDC, applied at concentrations that inhibit the above-mentioned CYP isoforms, potently (as compared to furafylline) inhibit human CYP1A2 and caffeine metabolism, in particular 1-N- and 3-N-demethylation.
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页码：1216 / 1220
页数：4
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