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Effect of Venlafaxine on the Pharmacokinetics of Risperidone
Author(s) -
Amchin Jess,
Zarycranski William,
Taylor Karen P.,
Albano Dominick,
Klockowski Patricia M.
Publication year - 1999
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127009903900314
Subject(s) - risperidone , venlafaxine , pharmacokinetics , active metabolite , pharmacology , cyp2d6 , dopamine antagonist , volume of distribution , medicine , chemistry , haloperidol , cytochrome p450 , schizophrenia (object oriented programming) , metabolism , dopamine , psychiatry , hippocampus , antidepressant
An open‐label study evaluated the effect of steady‐state venlafaxine on the single‐dose pharmacokinetic profile of risperidone, a CYP2D6 substrate; its active metabolite, 9‐hydroxyrisperidone; and the total active moiety (risperidone plus 9‐hydroxyrisperidone). Thirty healthy subjects received a 1 mg oral dose of risperidone before and after venlafaxine dosing to steady state. No significant changes occurred between treatments in the area under the concentration‐time curve (AUC) for 9‐hydroxyrisperidone or the total active moiety. However, venlafaxine weakly altered the pharmacokinetics of risperidone. Oral clearance decreased 38%, and the volume of distribution decreased 17%, resulting in a 32% increase in the AUC for risperidone. Renal clearance of 9‐hydroxyrisperidone also decreased by 20% in the presence of venlafaxine. Safety profiles of both drugs were not altered. This study demonstrated that venlafaxine did not affect the pharmacokinetic profile of 9‐hydroxyrisperidone or the total active moiety, although it weakly inhibited the metabolism of risperidone. These results show that venlafaxine is unlikely to be involved in a pharmacokinetic interaction with concomitant risperidone.