帕罗西汀对日本精神分裂症患者阿立哌唑及其活性代谢物脱氢阿立哌唑血浆浓度的影响。

Effects of paroxetine on plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, in Japanese patients with schizophrenia.

机构信息

Department of Neuropsychiatry, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.

出版信息

Ther Drug Monit. 2012 Apr;34(2):188-92. doi: 10.1097/FTD.0b013e31824a31e6.

DOI:10.1097/FTD.0b013e31824a31e6

PMID:22377745

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.

摘要

背景

研究了帕罗西汀共给药对 14 例精神分裂症日本患者阿立哌唑及其活性代谢物脱氢阿立哌唑血浆浓度的影响。

方法

这些患者已接受阿立哌唑（5 例 24mg/d，5 例 12mg/d，4 例 6mg/d）治疗至少 2 周。在第 1 周同时给予帕罗西汀 10mg/d，在第 2 周剂量增加至 20mg/d。在开始帕罗西汀前和帕罗西汀共给药后 1 周和 2 周各采集 3 次血样。在相同的日子里，使用临床总体印象和药物诱导的锥体外系症状量表分别评估疾病严重程度和锥体外系不良反应。使用液相色谱-质谱法测定阿立哌唑和脱氢阿立哌唑的血浆浓度。

结果

帕罗西汀共给药 10 和 20mg/d 时，阿立哌唑和阿立哌唑与脱氢阿立哌唑的总和血浆浓度显著升高（P < 0.05）（1.5 倍和 1.7 倍；1.4 倍和 1.5 倍）比帕罗西汀共给药前。帕罗西汀共给药 20mg/d 时，这些值也显著高于帕罗西汀共给药 10mg/d（1.1 倍和 1.1 倍）。整个研究期间，脱氢阿立哌唑的血浆浓度保持不变。帕罗西汀 10mg/d 时的平均临床总体印象评分显著高于共给药前（P < 0.05），而药物诱导的锥体外系症状量表评分在研究期间保持不变。