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Influence of CYP2D6 and CYP2C19 genotypes on venlafaxine metabolic ratios and stereoselective metabolism in forensic autopsy cases.
Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden; 3Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
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2015 (English)In: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 15, no 2, 165-71 p.Article in journal (Refereed) Published
Abstract [en]

We investigated whether polymorphisms in the CYP2D6 and CYP2C19 genes influence the metabolic ratios and enantiomeric S/R ratios of venlafaxine (VEN) and its metabolites O-desmethylvenlafaxine (ODV), N-desmethylvenlafaxine (NDV) and N,O-didesmethylvenlafaxine (DDV) in blood from forensic autopsy cases. In all, 94 postmortem cases found positive for VEN during toxicological screening were included. The CYP2D6 genotype was shown to significantly influence the ODV/VEN (P=0.003), DDV/NDV (P=0.010) and DDV/ODV (P=0.034) ratios. The DDV/ODV (P=0.013) and DDV/VEN (P=0.021) ratios were significantly influenced by the CYP2C19 genotype. The S/R ratios of VEN were significantly influenced by both CYP2D6 and CYP2C19 genotypes. CYP2D6 poor metabolizers (PMs) had lower S/R VEN ratios and CYP2C19 PMs had high S/R ratios of VEN in comparison. Our results show that the CYP2D6 genotype influences the O-demethylation whereas CYP2C19 influences the N-demethylation of VEN and its metabolites. In addition, we show a stereoselective metabolism where CYP2D6 favours the R-enantiomer whereas CYP2C19 favours the S-enantiomer.

Place, publisher, year, edition, pages
2015. Vol. 15, no 2, 165-71 p.
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Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:liu:diva-116540DOI: 10.1038/tpj.2014.50ISI: 000351780200008PubMedID: 25245581OAI: oai:DiVA.org:liu-116540DiVA: diva2:798870
Available from: 2015-03-27 Created: 2015-03-27 Last updated: 2017-12-04

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Karlsson, LouiseZackrisson, Anna LenaCarlsson, BjörnGreen, HenrikKugelberg, Fredrik C

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Karlsson, LouiseZackrisson, Anna LenaCarlsson, BjörnGreen, HenrikKugelberg, Fredrik C
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Department of Clinical PharmacologyDivision of Drug ResearchFaculty of Medicine and Health SciencesDepartment of Medical and Health Sciences
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The Pharmacogenomics Journal
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