Increase of Risperidone Concentration under Chlorprothixene Comedication - A Case Report

Risperidone is known to be metabolized by liver cytochrome P450 isoenzymes (CYP), primarily by CYP2D6 and to a much lesser extent also by CYP3A4, via aliphatic hydroxylation to form its active metabolite 9-hydroxyrisperidone. 9-Hydroxyrisperidone is the major metabolite and contributes equally to the pharmacological actions of risperidone. Therapeutic drug monitoring (TDM) under risperidone treatment refers to the sum of the risperidone and 9-hydroxyrisperidone concentrations as the so-called “active moiety”. Enzyme inhibition is said to have no effect on the concentration of the active moiety [6]. We report on a patient in whom the active moiety turned out to be too high in relation to the dose given. The patient was on risperidone in comedication with chlorprothixene. The concentration ratio of parent drug and active metabolite was increased as well suggesting a metabolic interaction of the two substances via enzyme inhibition.

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