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Pharmacogenetics of drug oxidation via cytochrome P450 (CYP) in the populations of Denmark, Faroe Islands and Greenland
- Source :
- Brøsen, K 2015, ' Pharmacogenetics of drug oxidation via cytochrome P450 (CYP) in the populations of Denmark, Faroe Islands and Greenland ', Drug Metabolism and Personalized Medicine, vol. 30, no. 3, pp. 147-163 . https://doi.org/10.1515/dmdi-2014-0029
- Publication Year :
- 2015
-
Abstract
- Denmark, the Faroe Islands and Greenland are three population-wise small countries on the northern part of the Northern Hemisphere, and studies carried out here on the genetic control over drug metabolism via cytochrome P450 have led to several important discoveries. Thus, CYP2D6 catalyzes the 2-hydroxylation, and CYP2C19 in part catalyzes the N-demethylation of imipramine. The phenomenon of phenocopy with regard to CYP2D6 was first described when Danish patients changed phenotype from extensive to poor metabolizers during treatment with quinidine. It was a Danish extensive metabolizer patient that became a poor metabolizer during paroxetine treatment, and this was due to the potent inhibition of CYP2D6 by paroxetine, which is also is metabolized by this enzyme. Fluoxetine and norfluoxetine are also potent inhibitors of CYP2D6, and fluvoxamine is a potent inhibitor of both CYP1A2 and CYP2C19. The bioactivation of proguanil to cycloguanil is impaired in CYP2C19 poor metabolizers. The O-demethylation of codeine and tramadol to their respective my-opioid active metabolites, morphine and (+)-O-desmethyltramadol was markedly impaired in CYP2D6 poor metabolizers compared to extensive metabolizers, and this impairs the hypoalgesic effect of the two drugs in the poor metabolizers. The frequency of CYP2D6 poor metabolizers is 2%–3% in Greenlanders and nearly 15% in the Faroese population. The frequency of CYP2C19 poor metabolizers in East Greenlanders is approximately 10%. A study in Danish mono and dizygotic twins showed that the non-polymorphic 3-N-demethylation of caffeine catalyzed by CYP1A2 is subject to approximately 70% genetic control.
- Subjects :
- Cycloguanil
CYP2D6
Proguanil
Denmark
Population
Cytochrome P-450 Enzyme System/genetics
Greenland
CYP2C19
Pharmacology
Inuits
Cytochrome P-450 Enzyme System
medicine
Atlantic Islands
Humans
Pharmacology (medical)
Pharmacokinetics
General Pharmacology, Toxicology and Pharmaceutics
education
skin and connective tissue diseases
Biotransformation
education.field_of_study
Polymorphism, Genetic
business.industry
CYP1A2
Inuit
business
Oxidation-Reduction
Pharmacogenetics
Drug metabolism
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Brøsen, K 2015, ' Pharmacogenetics of drug oxidation via cytochrome P450 (CYP) in the populations of Denmark, Faroe Islands and Greenland ', Drug Metabolism and Personalized Medicine, vol. 30, no. 3, pp. 147-163 . https://doi.org/10.1515/dmdi-2014-0029
- Accession number :
- edsair.doi.dedup.....f3e4f79a7a239a5da76f4367ce03e383