AI Article Synopsis
- The study evaluated the catalytic activities of 24 CYP2D6 variants specific to the Chinese population when metabolizing the drug atomoxetine, comparing them to the typical CYP2D6.1 variant.
- Using a baculovirus system to express these variants, researchers measured the formation of a metabolite (4-hydroxyatomoxetine) using advanced mass-spectrometry techniques.
- The results showed that many variants had significantly altered activity levels, with some increasing in efficiency while others decreased, highlighting the potential for personalized medicine in understanding drug metabolism in different individuals.
Article Abstract
Objective: The aim of this article was to assess the catalytic activities of 24 cytochrome P450 2D6 (CYP2D6) variants found in the Chinese population toward atomoxetine in vitro as well as CYP2D6.1.
Methods: In this study, the co-expression enzyme of human recombinant CYPOR, CYPb5, and CYP2D6.1 or other CYP2D6 variants with the baculovirus-mediated insect cells (Sf21) was used to study the catalytic activities of 24 CYP2D6 variants toward atomoxetine metabolism. The metabolite of atomoxetine (4-hydroxyatomoxetine) was detected by ultra-high performance liquid chromatography-mass spectrometry method.
Results: The intrinsic clearance (Vmax/Km) values of most variants were significantly altered when compared with CYP2D6.1. CYP2D6.94, CYP2D6.D336N, CYP2D6.R440C exhibited marked increased values 172, 126, 121% respectively. CYP2D6.89 and CYP2D6.98 exhibited similar catalytic activity as the wild type, whereas 17 variants exhibited significantly decreased values (from 5 to 87%) due to increase Km and/or decrease Vmax values. However, CYP2D6.92 and CYP2D6.96 showed no or few activity because of producing nothing.
Conclusions: Our results suggest that most of these newly found variants exhibit significantly changed catalytic activities compared with the wild type. And these findings provide valuable information for the growth and development of personalized medicine in China.
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| http://dx.doi.org/10.1159/000442952 | DOI Listing |
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