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Effects of Paroxetine on Plasma Concentrations of Aripiprazole and Its Active Metabolite, Dehydroaripiprazole, in Japanese Patients With Schizophrenia

Nemoto, Kenji MD*; Mihara, Kazuo MD, PhD*; Nakamura, Akifumi MD, PhD*; Nagai, Goyo MD, PhD*; Kagawa, Shoko MD*; Suzuki, Takeshi PhD; Kondo, Tsuyoshi MD, PhD*

Therapeutic Drug Monitoring:
doi: 10.1097/FTD.0b013e31824a31e6
Original Article
Abstract

Background: The effects of paroxetine coadministration on plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, were studied in 14 Japanese patients with schizophrenia.

Methods: The patients had been treated with aripiprazole (24 mg/d in 5 cases, 12 mg/d in 5 cases, and 6 mg/d in 4 cases) for at least 2 weeks. Paroxetine 10 mg/d was coadministered during the first week, and the dose was increased to 20 mg/d during the second week. Blood samples were taken 3 times, before the start of paroxetine and then 1 and 2 weeks after paroxetine coadministration. On the same days, the severity of illness and extrapyramidal adverse effects were evaluated by the clinical global impressions and the Drug-Induced Extra-Pyramidal Symptoms Scale, respectively. Plasma concentrations of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass spectrometric detection.

Results: Plasma concentrations of aripiprazole and the sum of aripiprazole and dehydroaripiprazole during coadministration of paroxetine 10 and 20 mg/d were significantly (P < 0.05) higher (1.5-fold and 1.7-fold; 1.4-fold and 1.5-fold) than those before paroxetine coadministration. Those values during coadministration of paroxetine 20 mg/d were also significantly (P < 0.05) higher (1.1-fold and 1.1-fold) than those during coadministration of paroxetine 10 mg/d. Plasma concentrations of dehydroaripiprazole were unchanged throughout the study period. The mean clinical global impression score was significantly (P < 0.05) higher during the paroxetine 10 mg/d than that before coadministration, whereas the Drug-Induced Extra-Pyramidal Symptoms Scale scores remained unchanged during the study.

Conclusions: This study suggests that lower doses (10–20 mg/d) of paroxetine coadministration increase plasma concentrations of aripiprazole and the sum of aripiprazole and dehydroaripiprazole.

Author Information

*Departments of Neuropsychiatry

Pharmacy, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.

Supported by Grant-in Aids from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (#16790696 and #19591366). Authentic aripiprazole and dehydroaripiprazole were kindly provided by Otsuka Pharmaceutical, Co, Ltd, Tokyo, Japan.

The authors declare no conflict of interest.

Correspondence: Kazuo Mihara, MD, PhD, Department of Neuropsychiatry, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa 903-0215, Japan (e-mail: miharak@med.u-ryukyu.ac.jp).

Received November 14, 2011

Accepted January 9, 2012

© 2012 Lippincott Williams & Wilkins, Inc.