联合用药精神障碍患者氯氮平血药浓度监测

Detection of plasma clozapine concentration in psychosis disorder inpatients receiving comedications

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。

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 elozapine combined with other antipsychotics, so as to timely regulate the dosage of CLZ.