{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:53:30Z","timestamp":1791280410008,"version":"4.1.0"},"reference-count":41,"publisher":"Walter de Gruyter GmbH","issue":"3","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_dmpt-2026-0018_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Reports on drug-drug interactions between valproic acid (VPA) and clozapine (CLZ) are very inconsistent. Previous reports demonstrate that VPA may exhibit either inhibitory or inductive effects or have no effect on CLZ pharmacokinetics. The aim of this study was to investigate the impact of VPA on plasma CLZ concentrations in a series of Tunisian patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmpt-2026-0018_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study was conducted from 2010 to 2025 at the Clinical Pharmacology Department of the Tunisian National Pharmacovigilance Center and included samples of patients treated by CLZ for schizophrenia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmpt-2026-0018_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 1,035 samples were analyzed: 814 corresponded to CLZ monotherapy and 221 to combined of VPA and CLZ therapy. The median CLZ plasma concentration-to-dose ratio (C\/D ratio) was significantly higher in the monotherapy group than in the combination group (0.87 vs. 0.75\u202fng\/mL per mg\/day; p&lt;0.05). Within the combination group, the CLZ C\/D ratio was significantly lower in men than in women (0.67 vs. 1.16\u202fng\/mL per mg\/day; p&lt;0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmpt-2026-0018_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study demonstrates a significant inductive effect of VPA on CLZ metabolism, which may be influenced by factors such as gender. Hence, clinicians should be aware of the critical need for CLZ monitoring in clinical practice to personalize treatment adjustment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/dmpt-2026-0018","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:13:28Z","timestamp":1787562808000},"page":"183-188","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of the impact of valproic acid co-administration on clozapine plasma concentrations in Tunisian patients"],"prefix":"10.1515","volume":"41","author":[{"given":"Syrine","family":"Ben Hammamia","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology , National Center Chalbi Belkahia of Pharmacovigilance , Tunis , Tunisia"},{"name":"Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02) , Tunis , Tunisia"},{"name":"University of Tunis El Manar, Faculty of Medicine of Tunis , Tunis , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5362-3921","authenticated-orcid":false,"given":"Safa","family":"Souissi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology , National Center Chalbi Belkahia of Pharmacovigilance , Tunis , Tunisia"},{"name":"Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02) , Tunis , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariem","family":"Bettoumia","sequence":"additional","affiliation":[{"name":"University of Monastir, Faculty of Pharmacy of Monastir , Monastir , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouna","family":"Ben Sassi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology , National Center Chalbi Belkahia of Pharmacovigilance , Tunis , Tunisia"},{"name":"Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02) , Tunis , 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Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanene","family":"El Jebari","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology , National Center Chalbi Belkahia of Pharmacovigilance , Tunis , Tunisia"},{"name":"Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02) , Tunis , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Zouari","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology , National Center Chalbi Belkahia of Pharmacovigilance , Tunis , Tunisia"},{"name":"Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02) , Tunis , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issam","family":"Salouage","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology , National Center Chalbi Belkahia of Pharmacovigilance , Tunis , Tunisia"},{"name":"Research Laboratory of 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