Plasma concentrations of risperidone and olanzapine during coadministration with oxcarbazepine.
OBJECTIVE
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.
Rosaria Muscatello
Maria
M
Department of Neurosciences, Psychiatric and Anesthesiological Sciences, University of Messina, Italy.
Pacetti
Monica
M
Cacciola
Massimo
M
La Torre
Diletta
D
Zoccali
Rocco
R
D'Arrigo
Concetta
C
Migliardi
Gaetana
G
Spina
Edoardo
E
D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000097:blood* / Q000627:therapeutic use; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D000078330:Oxcarbazepine; D018967:Risperidone / Q000097:blood* / Q000627:therapeutic use
D000927:Anticonvulsants; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D002220:Carbamazepine; D003577:Cytochrome P-450 Enzyme System; D018967:Risperidone; D000077152:Olanzapine; D000078330:Oxcarbazepine