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Ther Drug Monit. 2013 Oct;35(5):649-52. doi: 10.1097/FTD.0b013e3182966c2f.

Interaction between paliperidone and carbamazepine.

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1
Department of Neuropsychiatry, Graduate School of Medicine, Hirosaki University, Hirosaki, Japan.

Abstract

BACKGROUND:

This aim of this study was to determine the impact of carbamazepine on the pharmacokinetics of paliperidone.

METHODS:

Six schizophrenic patients initially received a 6-12 mg/d dose of paliperidone alone. Subsequently, a 200 mg/d dose of carbamazepine was administered, and the carbamazepine dose was increased to 400 mg/d and then 600 mg/d. Plasma concentrations of paliperidone before and after carbamazepine coadministration were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS).

RESULTS:

Carbamazepine significantly reduced the plasma concentration of paliperidone. The plasma concentration of paliperidone at baseline and with coadministration of 200, 400, and 600 mg/d were 45.8 ± 11.7, 26.9 ± 13.7, 17.1 ± 8.2, and 15.9 ± 7.6 ng/mL, respectively. The concentration of paliperidone with carbamazepine coadministration at doses of 200, 400, and 600 mg/d were 55.7% ± 20.7%, 36.1% ± 12.2%, and 33.6% ± 10.4%, respectively, of baseline. This effect occurred even at the carbamazepine dose of 200 mg/d and reached a plateau at doses higher than 400 mg/d. However, carbamazepine coadministration exacerbated the psychotic symptoms in some patients.

CONCLUSIONS:

The results of the present study suggest that adjunctive treatment with carbamazepine reduces the concentration of paliperidone in a dose-dependent manner, most likely because of the induction of several drug-metabolizing enzymes and several drug transporters.

PMID:
24052066
DOI:
10.1097/FTD.0b013e3182966c2f
[Indexed for MEDLINE]
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