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Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):439-52. doi: 10.1517/17425255.4.4.439 .

P450 oxidoreductase: genetic polymorphisms and implications for drug metabolism and toxicity.

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1
University of Kansas Medical Center, Department of Pharmacology, Toxicology, and Therapeutics, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA.

Abstract

BACKGROUND:

Cytochrome P450 oxidoreductase (POR) is the only electron donor for all microsomal cytochrome P450 monooxygenases (CYP), some of which are phase I drug-metabolizing enzymes, responsible for oxidation of more than 80% of drugs.

OBJECTIVES:

To provide a more thorough understanding of the genetic factors influencing drug metabolism, we address the role of genetic polymorphisms in the POR gene, and their implications for drug metabolism and cytotoxicity.

METHODS:

The scope of this review is intended to cover polymorphisms currently identified in the POR gene, assess their functional significance on POR activity, and address their impact on CYP-mediated drug metabolism. POR is also responsible for directly metabolizing several anticancer prodrugs via a 1-electron reduction reaction, so the effect of POR polymorphisms on the direct bioactivation of drugs is also considered.

RESULTS/CONCLUSION:

POR is a polymorphic enzyme that can affect CYP-mediated drug metabolism as well as direct bioactivation of prodrugs. Genetic polymorphisms in the POR gene may help to explain altered drug-metabolizing phenotypes.

PMID:
18433346
DOI:
10.1517/17425255.4.4.439
[Indexed for MEDLINE]
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