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Plasma Concentrations of Risperidone and Olanzapine during Coadministration with Oxcarbazepine
Author(s) -
Rosaria Muscatello Maria,
Pacetti Monica,
Cacciola Massimo,
La Torre Diletta,
Zoccali Rocco,
Arrigo Concetta D',
Migliardi Gaetana,
Spina Edoardo
Publication year - 2005
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2005.71104.x
Subject(s) - oxcarbazepine , risperidone , carbamazepine , olanzapine , pharmacology , active metabolite , dopamine antagonist , medicine , psychology , chemistry , pharmacokinetics , schizophrenia (object oriented programming) , psychiatry , dopamine , haloperidol , epilepsy
Summary: Purpose: Oxcarbazepine (OZC) is a second‐generation antiepileptic drug (AED) that also may be used as a mood stabilizer. Unlike carbamazepine (CBZ), which is an inducer of the cytochrome P‐450 isoforms and may accelerate the elimination of several therapeutic agents, OXC seems to have only a modest inducing action. The aim of this investigation was to evaluate the effect of a treatment with OXC on plasma concentrations of the new antipsychotics risperidone and olanzapine. Methods: OXC, at a dosage of 900–1,200 mg/day, was administered for 5 consecutive weeks to 25 outpatients, 10 men and 15 women, aged 25 to 64 years, with bipolar or schizoaffective disorder. Twelve patients were stabilized on risperidone therapy (2–6 mg/day) and 13 on olanzapine (5–20 mg/day). Steady‐state plasma concentrations of risperidone and its active metabolite 9‐hydroxyrisperidone (9‐OH‐risperidone) and olanzapine were measured by high‐pressure liquid chromatography (HPLC) before addition of OXC and after 5 weeks from the start of adjunctive treatment. Results: OXC caused only minimal and no significant changes in the mean plasma levels of risperidone (from 5.6 ± 3.6 ng/ml at baseline to 4.8 ± 2.6 ng/ml at week 5), 9‐OH‐risperidone (from 23.6 ± 7.5 to 24.7 ± 7.4 ng/ml), and olanzapine (from 26.5 ± 5.7 ng/ml at baseline to 27.8 ± 5.1 ng/ml). OXC coadministration with either risperidone or olanzapine was well tolerated. Conclusions: Our findings indicate that OXC does not affect the elimination of risperidone and olanzapine, thus confirming its weak inducing effect on hepatic drug‐metabolizing enzymes.