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Assessment of the impact of valproic acid co-administration on clozapine plasma concentrations in Tunisian patients

Syrine Ben Hammamia, Safa Souissi, Mariem Bettoumia, Mouna Ben Sassi, Khouloud Ferchichi, Mouna Daldoul, Hanene El Jebari, Mohamed Zouari, Issam Salouage, Rim Charfi, Riadh Daghfous, Emna Gaies, Sameh Trabelsi

Drug Metabolism and Personalized Therapy · 2026

Vollständiger Abstract

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Abstract Objectives 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. Methods 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. Results 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 ng/mL per mg/day; p

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Autor:innen
Syrine Ben Hammamia, Safa Souissi, Mariem Bettoumia, Mouna Ben Sassi, Khouloud Ferchichi, Mouna Daldoul, Hanene El Jebari, Mohamed Zouari, Issam Salouage, Rim Charfi, Riadh Daghfous, Emna Gaies, Sameh Trabelsi
Quelle
Drug Metabolism and Personalized Therapy
Publikation
2026-01-01
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ISSN / ISBN
2363-8915
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Syrine Ben Hammamia, Safa Souissi, Mariem Bettoumia, Mouna Ben Sassi, Khouloud Ferchichi, Mouna Daldoul, Hanene El Jebari, Mohamed Zouari, Issam Salouage, Rim Charfi, Riadh Daghfous, Emna Gaies, Sameh Trabelsi (2026). Assessment of the impact of valproic acid co-administration on clozapine plasma concentrations in Tunisian patients. Drug Metabolism and Personalized Therapy. https://doi.org/10.1515/dmpt-2026-0018
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