The role of CYP2C9 genetic polymorphism in carvedilol O-desmethylation in vitro.

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Pan PP, Weng QH, Zhou CJ, Wei YL, Wang L, Dai DP, Cai JP, Hu GX

The role of CYP2C9 genetic polymorphism in carvedilol O-desmethylation in vitro.

Eur J Drug Metab Pharmacokinet. 2016 Feb;41(1):79-86. doi: 10.1007/s13318-014-0245-2. Epub 2014 Dec 5.

PubMed ID

25476996 [ View in PubMed

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Abstract

We aimed at investigating the role of CYP2C9 in carvedilol O-desmethylation and identifying the effect of 35 CYP2C9 allelic variants we found in Chinese Han population on the in vitro metabolism of carvedilol. Recombinant CYP2C9 and CYP2D6 microsomes of the wild type were used to test and verify the enzymes involved in carvedilol O-desmethylation. Recombinant CYP2C9 microsomes of distinguished genotypes were used to characterize the corresponding enzyme activity toward carvedilol. 2-100 muM carvedilol was incubated for 30 min at 37 degrees C. The products were detected using high-performance liquid chromatography. CYP2C9 plays a certain role in carvedilol metabolism. Compared with wild-type CYP2C9*1, the intrinsic clearance (V max/K m) values of all variants toward carvedilol O-desmethylation were significantly altered. The variants exhibited significantly decreased values (from 30 to 99.8 %) due to increased K m and/or decreased V max values. We conclude that recombinant system could be used to investigate the enzymes involved in drug metabolism and these findings complement the database where CYP2C9 polymorphism interacts with biotransformation of exogenous substances like drugs and toxins.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Carvedilol	Cytochrome P450 2C9	Protein	Humans	Unknown	Substrate	Details