Show simple item record

dc.contributor.authorWollmann, Birgit Malene Tovik
dc.contributor.authorSmith, Robert Løvsletten
dc.contributor.authorKringen, Marianne K.
dc.contributor.authorIngelman-Sundberg, Magnus
dc.contributor.authorMolden, Espen
dc.contributor.authorStørset, Elisabet
dc.identifier.citationBritish Journal of Clinical Pharmacology. 2023, .en_US
dc.description.abstractAims: The extensive variability in cytochrome P450 2D6 (CYP2D6) metabolism is mainly caused by genetic polymorphisms. However, there is large, unexplained variability in CYP2D6 metabolism within CYP2D6 genotype subgroups. Solanidine, a dietary compound found in potatoes, is a promising phenotype biomarker predicting individual CYP2D6 metabolism. The aim of this study was to investigate the correlation between solanidine metabolism and the CYP2D6-mediated metabolism of risperidone in patients with known CYP2D6 genotypes. Methods: The study included therapeutic drug monitoring (TDM) data from CYP2D6-genotyped patients treated with risperidone. Risperidone and 9-hydroxyrisperidone levels were determined during TDM, and reprocessing of the respective TDM full-scan high-resolution mass spectrometry files was applied for semi-quantitative measurements of solanidine and five metabolites (M402, M414, M416, M440 and M444). Spearman's tests determined the correlations between solanidine metabolic ratios (MRs) and the 9-hydroxyrisperidone-to-risperidone ratio. Results: A total of 229 patients were included. Highly significant, positive correla- tionswere observed between all solanidine MRs and the 9-hydroxyrisperidone-to- risperidone ratio (ρ > 0.6, P < .0001). The strongest correlation was observed for the M444-to-solanidine MR in patients with functional CYP2D6 metabolism, i.e., genotype activity scores of 1 and 1.5 (ρ 0.72–0.77, P < .0001). Conclusion: The present study shows strong, positive correlations between solanidine metabolism and CYP2D6-mediated risperidone metabolism. The strong correlation within patients carrying CYP2D6 genotypes encoding functional CYP2D6 metabolism suggests that solanidine metabolism may predict individual CYP2D6 metabolism, and hence potentially improve personalized dosing of drugs metabolized by CYP2D6.en_US
dc.rightsNavngivelse-Ikkekommersiell 4.0 Internasjonal*
dc.titleEvidence for solanidine as a dietary CYP2D6 biomarker: Significant correlation with risperidone metabolismen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.source.journalBritish Journal of Clinical Pharmacologyen_US

Files in this item


This item appears in the following Collection(s)

Show simple item record

Navngivelse-Ikkekommersiell 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse-Ikkekommersiell 4.0 Internasjonal