{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:01:50Z","timestamp":1785402110058,"version":"3.56.0"},"reference-count":45,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["INST 105022\/100-1 LAGG"],"award-info":[{"award-number":["INST 105022\/100-1 LAGG"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"award":["INST 105022\/100-1 LAGG"],"award-info":[{"award-number":["INST 105022\/100-1 LAGG"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Sex-specific differences in the pharmacokinetics of psychotropic drugs are gaining increasing clinical relevance, but only limited data are currently available on sex-specific effects within genetically defined metabolizer phenotype categories. The objective of this study was to assess genotype-dependent sex differences in the metabolic capacity of the drug-metabolizing enzymes CYP2D6 and CYP2C19. Methods: Statistical analyses were performed using linear mixed-effects models with subject-level random intercepts to account for repeated therapeutic drug monitoring (TDM) measurements. Venlafaxine and risperidone were used as probe drugs to find differences in the metabolic capacity of CYP2D6 and escitalopram for CYP2C19. Pharmacokinetic surrogate parameters were the metabolite-to-parent ratio (MPR) for venlafaxine and risperidone and the dose-corrected serum concentration (CD) for escitalopram. Models included sex, metabolizer phenotype, and their interaction, adjusted for age and creatinine production rate (CPR). Sex-specific differences within phenotype groups were assessed using estimated marginal means. Results: Among venlafaxine samples (N = 117) and risperidone samples (N = 73), no significant sex-specific differences in MPR were observed within CYP2D6 metabolizer groups. For escitalopram samples (N = 51), a significant sex difference was observed among CYP2C19 normal metabolizers (NMs), with higher CD in males compared to females. Conclusions: Exploratory analyses suggested a higher metabolic capacity in CYP2C19 NM females treated with escitalopram. Due to the limited sample size, however, this finding should be considered hypothesis-generating. Future studies in larger samples are needed to corroborate whether sex and other factors modulate the metabolic capacity of CYP2C19, e.g., by epigenetic mechanisms.<\/jats:p>","DOI":"10.3390\/genes17060718","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T08:14:12Z","timestamp":1782375252000},"page":"718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preliminary Evidence for Sex Differences in CYP2C19 Metabolic Capacity During Psychotropic Drug Treatment"],"prefix":"10.3390","volume":"17","author":[{"given":"Janina","family":"Eiberger","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9421-1292","authenticated-orcid":false,"given":"Heike","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Reif","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, 60528 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Deckert","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"Institute of Clinical Epidemiology and Biometry, Julius-Maximilians-Universit\u00e4t W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4026-3561","authenticated-orcid":false,"given":"Sebastian","family":"Walther","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8355-8584","authenticated-orcid":false,"given":"Martina","family":"Hahn","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, 60528 Frankfurt, Germany"},{"name":"Department of Mental Health, Varisano Hospital Frankfurt Hoechst, 65929 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4780-612X","authenticated-orcid":false,"given":"Maike","family":"Scherf-Clavel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.2165\/00003088-200948030-00001","article-title":"Sex differences in pharmacokinetics and pharmacodynamics","volume":"48","author":"Soldin","year":"2009","journal-title":"Clin. 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