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联合用药精神障碍患者氯氮平血药浓度监测
蒋平1,刘红梅1,任娟娟1,李婷2,林治光1,金一3,崔慧茹1,孙秀佳1,李春波1*
0
(1. 上海交通大学医学院附属上海市精神卫生中心生化药理研究室,上海 200030
2. 浙江省嘉兴市康慈医院,嘉兴 314500
3. 中国科学院心理研究所,北京 100101
*通信作者)
摘要:
目的 考察联合用药对精神障碍患者氯氮平(CLZ) 血药浓度的影响。方法 应用高效液相色谱法(HPLC) 测定571例服用CLZ的住院精神障碍患者CLZ及去甲氯氮平(N-CLZ) 的血药浓度;并结合CLZ剂量、联合用药(氯硝西泮等12种药物)等情况,运用SPSS 17.0软件包分析联合用药对CLZ血药浓度的影响。结果 联合用药组CLZ剂量、CLZ血药浓度、N-CLZ血药浓度均低于CLZ单用组, 差异有统计学意义(P<0.01)。其中联用氯硝西泮、帕罗西汀、文拉法新、阿立哌唑、喹硫平和利培酮组的CLZ使用剂量低于CLZ单用组,差异有统计学意义(P<0.05,P<0.01);联用氯硝西泮、碳酸锂、丙戊酸钠和喹硫平组的CLZ血药浓度低于CLZ单用组, 差异有统计学意义(P<0.05,P<0.01);联用氯硝西泮、碳酸锂、丙戊酸钠、舍曲林、喹硫平和利培酮组的N-CLZ血药浓度低于CLZ单用组, 差异有统计学意义(P<0.05,P<0.01)。Spearman等级相关分析显示:CLZ单用组中,CLZ剂量与CLZ血药浓度、N-CLZ血药浓度三者间两两呈正相关(P<0.05,P<0.01)。结论 一些常用精神科药物对氯氮平的血药浓度存在一定程度影响,临床上应加强对联合用药精神障碍患者氯氮平血药浓度监测,及时调整患者的氯氮平剂量。
关键词:  血药浓度  联合药物疗法  氯氮平  去甲氯氮平
DOI:
投稿时间:2013-01-05修订日期:2013-05-27
基金项目:国家自然科学基金(81171267),上海市精神卫生中心院级课题(2012-YJ-09).
Detection of plasma clozapine concentration in psychosis disorder inpatients receiving comedications
JIANG Ping1,LIU Hong-mei1,REN Juan-juan1,LI Ting2,LIN Zhi-guang1,JIN Yi3,CUI Hui-ru1,SUN Xiu-jia1,LI Chun-bo1*
(1. Department of Biochemistry and Psychopharmacology, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, China
2. Jiaxing Kangci Hospital, Jiaxing 314500, Zhejiang, China
3. Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China
*Corresponding author.)
Abstract:
Objective To investigate the effect of various comedications on the plasma concentration of clozapine(CLZ) in inpatients with psychosis disorder. Methods High performance liquid chromatography (HPLC) was used to analyze serum CLZ and norclozapine(N-CLZ) concentrations in 571 psychosis patients. The influence of commedication on plasma CLZ concentration was analyzed using SPSS 17.0 software while considering the dosage of CLZ and the comedications with 12 drugs most often used in combination with CLZ. Results The CLZ dosage, plasma CLZ concentration and plasma N-CLZ concentration in the comedication group were significantly lower than those in pure CLZ group (P<0.01). The CLZ dosage in groups of comedications with clonazepam, paroxetine, venlafaxine, aripiprazole, quetiapine and risperidone were significantly lower than that of pure CLZ group (P<0.05,P<0.01). Comedication with clonazepam, lithium carbonate, valproate and quetiapine significantly decreased the plasma concentration of CLZ (P<0.05,P<0.01). Comedication with clonazepam, lithium carbonate, valproate, sertraline, quetiapine and risperidone significantly decreased the plasma concentration of N-CLZ (P<0.05,P<0.01). Spearman’s correlation analysis found that there were significant positive correlations among any two of dosage CLZ, concentration of CLZ and concentration of N-CLZ in CLZ group (P<0.05,P<0.01). Conclusion Some commonly-used antipsychotics have impact on plasma CLZ concentration. Drug monitoring and dosage regulation of CLZ should be stressed among patients comedicated with clozapine combined with other antipsychotics, so as to timely regulate the dosage of CLZ.
Key words:  plasma concentration  combination drug therapy  clozapine  norclozapine