Relation between genotype, phenotype and therapeutic drug concentrations of nortriptyline or venlafaxine users in old age psychiatryBerm, E. J. J., Kok, R. M., Hak, E. & Wilffert, B., 1-Feb-2015, In : Naunyn-Schmiedeberg's Archives of Pharmacology. 388, 1, p. 52-53 2 p.
Research output: Contribution to journal › Meeting Abstract › Academic
Background The relationship between phenotype and genotype of the polymorphic cytochrome P450 2D6 enzyme (CYP2D6) has been intensively studied, however few studies are conducted among older persons. In a study among 900 relatively young venlafaxine users (mean age 45 years), 83% were genotyped as an extensive metabolizer (EM), but 21% were observed to have a poor metabolizer (PM) phenotype (1). This so-called 'phenoconversion' is one of the reasons for clinicians to mainly rely on therapeutic drug monitoring (TDM) as a sufficient indicator for genotype and to adjust the drug dosage if indicated. We determined associations between blood drug levels, genotype and phenotype in an old age sample of patients treated for depression with nortriptyline (NTP) or venlafaxine (VFX). Methods We analyzed post-hoc data from a clinical trial among older starters of NTP or VFX (2). The study population was monitored by TDM for twelve weeks. The drug levels of NTP and VFX as well as the main CYP2D6 metabolites, OH-nortriptyline and O-desmethylvenlafaxine, were measured. In addition, the genotypes for the CYP2D6 ∗3 and ∗4 alleles were available. We sub-grouped the data into phenotypes according to the metabolite/mother compound ratio. Next, we compared the phenotype with the genotype results and translated the blood levels into clinical outcomes being below, above, or within drug-specific therapeutic windows according to guidelines and tested for significant (p
|Number of pages||2|
|Journal||Naunyn-Schmiedeberg's Archives of Pharmacology|
|Publication status||Published - 1-Feb-2015|
- nortriptyline, venlafaxine, desvenlafaxine, enzyme, cytochrome P450, cytochrome, phenotype, drug concentration, senescence, psychiatry, genotype, human, patient, drug blood level, population, clinical trial, drug dose, drug monitoring, blood sampling, blood level, allele, metabolite