کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5807432 | 1113399 | 2016 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Effect of CYP2D6 genetic polymorphism on the metabolism of citalopram in vitro
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Genetic polymorphisms of CYP2D6 significantly influence the efficacy and safety of some drugs, which might cause adverse effects and therapeutic failure. We aimed at investigating the role of CYP2D6 in the metabolism of citalopram and identifying the effect of 24 CYP2D6 allelic variants we found in Chinese Han population on the metabolism of citalopram in vitro. These CYP2D6 variants expressed by insect cells system were incubated with 10-1000 μM citalopram for 30 min at 37 °C and the reaction was terminated by cooling to â80 °C immediately. Citalopram and its metabolites were analyzed by high-performance liquid chromatography (HPLC). The intrinsic clearance (Vmax/Km) values of the variants toward citalopram metabolites were significantly altered, 38-129% for demethylcitalopram and 13-138% for citalopram N-oxide when compared with CYP2D6*1. Most of the tested rare alleles exhibited significantly decreased values due to increased Km and/or decreased Vmax values. We conclude that recombinant system could be used to investigate the enzymes involved in drug metabolism and these findings suggest that more attention should be paid to subjects carrying these CYP2D6 alleles when administering citalopram in the clinic.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Drug Metabolism and Pharmacokinetics - Volume 31, Issue 2, April 2016, Pages 133-138
Journal: Drug Metabolism and Pharmacokinetics - Volume 31, Issue 2, April 2016, Pages 133-138
نویسندگان
Xiao-xia Hu, Ling-jing Yuan, Ping Fang, Yong-Hui Mao, Yun-yun Zhan, Xiang-yu Li, Da-Peng Dai, Jian-Ping Cai, Guo-Xin Hu,