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The aim of this study was to detect and determine phenoconversion using the solanidine metabolites 3,4\u2010seco\u2010solanidine\u20103,4\u2010dioic acid (SSDA) and 4\u2010OH\u2010solanidine as diet\u2010derived cytochrome P450 2D6 (CYP2D6) biomarkers in a geriatric, multimorbid cohort with high levels of polypharmacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Blood samples and data of geriatric, multimedicated patients were collected during physician counsel (CT: NCT05247814). Solanidine and its metabolites were determined via liquid chromatography\/tandem mass spectrometry and used for CYP2D6 phenotyping. CYP2D6 genotyping was performed and activity scores (AS) were assigned. Complete medication intake was assessed. A shift of the AS predicted via genotyping as measured by phenotyping was calculated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Solanidine and its metabolites were measured in 88 patients with complete documentation of drug use. Patients had a median age of 83\u2009years (interquartile range [IQR] 77\u201087) and the majority (70.5%, n\u2009=\u200962) were female. Patients took a median of 15 (IQR 12\u201017) medications. The SSDA\/solanidine metabolic ratio correlated significantly with the genotyping\u2010derived AS (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u2009.001) and clearly detected poor metabolizers. In the model adjusted for age, sex, Charlson Comorbidity Index and estimated glomerular filtration rate each additional CYP2D6 substrate\/inhibitor significantly lowered the expected AS by 0.53 (95% confidence interval 0.85\u20100.21) points in patients encoding functional CYP2D6 variants (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00.242).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Phenotyping of CYP2D6 activity by measurement of diet\u2010derived biomarkers elucidates phenoconversion in geriatric patients. These results might serve as a prerequisite for the validation and establishment of a bedside method to measure CYP2D6 activity in multimorbid patients for successful application of personalized drug prescribing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70004","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:49:19Z","timestamp":1739753359000},"page":"1842-1852","source":"Crossref","is-referenced-by-count":14,"title":["Solanidine\u2010derived CYP2D6 phenotyping elucidates phenoconversion in multimedicated geriatric patients"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9379-4745","authenticated-orcid":false,"given":"Jens Andreas","family":"Sar\u00f6mba","sequence":"first","affiliation":[{"name":"Institute of Clinical Pharmacology University Hospital RWTH Aachen  Aachen North Rhine\u2010Westphalia 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