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Un rapport CLZ/DMC élevé serait associé à une meilleure tolérance. Le polymorphisme génétique CYP1A2*1F (présent à 68% dans la population caucasienne) entraîne une augmentation de l'activité enzymatique. A l'état homozygote il serait associé à une moins bonne réponse à la clozapine, surtout chez les fumeurs. La fluvoxamine est un antidépresseur inhibiteur de la recapture de sérotonine ayant une action ,
Il a été constaté chez ces patients une corrélation entre la diminution du rapport CLZ/DMC et la consommation de tabac, de façon dose-dépendante. L'association à la fluvoxamine était corrélée à une augmentation dose-dépendante des rapports Concentration/Dose en clozapine et CLZ/DMC. Une évolution défavorable de la tolérance globale était corrélée à la clozapinémie ,
, La pharmacogénétique de la clozapine et son association à la fluvoxamine s'intègrent dans une approche de médecine personnalisée, afin d'individualiser le traitement des patients atteints de schizophrénie résistante, et ainsi de favoriser l'efficacité et de limiter les effets secondaires