Significantly lower CYP2D6 metabolism measured as the O/N ‐desmethylvenlafaxine metabolic ratio in carriers of CYP2D6*41 versus CYP2D6*9 or CYP2D6*10 : a study on therapeutic drug monitoring data from 1003 genotyped Scandinavian patients
| Autor: | Marin M. Jukic, Tore Haslemo, Erik Eliasson, Espen Molden, Magnus Ingelman-Sundberg |
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| Rok vydání: | 2018 |
| Předmět: |
Pharmacology
CYP2D6 medicine.medical_specialty Multivariate analysis medicine.diagnostic_test business.industry Null (mathematics) digestive system 030226 pharmacology & pharmacy Gastroenterology 03 medical and health sciences 0302 clinical medicine Therapeutic drug monitoring Internal medicine Genotype Linear regression Medicine Biomarker (medicine) Pharmacology (medical) 030212 general & internal medicine Allele skin and connective tissue diseases business |
| Zdroj: | British Journal of Clinical Pharmacology. 85:194-201 |
| ISSN: | 1365-2125 0306-5251 |
| Popis: | AIMS CYP2D6*9, CYP2D6*10 and CYP2D6*41 are the most frequent reduced-function CYP2D6 alleles in Caucasians. Despite lacking in vivo evidence, they are collectively classified with an enzyme activity score of 0.5. Thus, the aim of this study was to compare the functional impact of CYP2D6*9, CYP2D6*10 and CYP2D6*41 on CYP2D6 metabolism in a large patient population. METHODS A total of 1003 patients (mainly Caucasians) with data on CYP2D6 genotype and serum concentrations of venlafaxine and metabolites were included from a therapeutic drug monitoring service in Oslo, Norway. The O-desmethyl-to-N-desmethyl-venlafaxine metabolic ratio (MR) was applied as CYP2D6 biomarker and compared (Mann-Whitney) between carriers of CYP2D6*9-10 (merged) and CYP2D6*41, either combined with CYP2D6*1 or non-coding (null) alleles. MR subgroup estimates were obtained by multiple linear regression for calculations of CYP2D6*9-10 and CYP2D6*41 activity scores. RESULTS MR was significantly lower in carriers of CYP2D6*41 than CYP2D6*9-10 (P |
| Databáze: | OpenAIRE |
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