联用氯硝西泮对精神分裂症患者氯氮平、N-去甲氯氮平血药浓度影响的回顾性研究（英文）  

Effect of clonazepam co-administered with clozapine on the serum clozapine and norclozapine concentration of patients with schizophrenia:A Retrospective Survey

作　　者：蒋平 林治光 金一 任娟娟 刘红梅 崔慧茹 王继军 李春波 

机构地区：[1]Shanghai Key Laboratory of Psychotic Disorders,Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine [2]Postcode:200030 [3]Institute of Psychology,Chinese Academy of Sciences [4]Postcode:100101

出　　处：《上海精神医学》2016年第6期318-325,共8页Shanghai Archives of Psychiatry

基　　金：The National Natural Science Fund(No.81171267);National Basic Research Program of China(No.2007CB512306);Shanghai Key Laboratory of Psychotic Disorders(No.13dz2260500);Shanghai Program for Fostering Scientific Leaders in Health(No.XBR2011005)

摘　　要：背景:对精神分裂症患者,氯氮平(CLZ)有时是与氯硝西泮(CLNAZ)联合使用的。然而,联用氯硝西泮(CLNAZ)和氯氮平(CLZ)对氯氮平和主要代谢产物N-去甲氯氮平(N-CLZ)的血清浓度的影响尚不清楚。目标:调查联用氯硝西泮(CLNAZ)对精神分裂症患者氯氮平(CLZ)血药浓度的影响。方法:应用高效液相色谱技术(HPLC)测定341例服用CLZ的住院精神分裂症患者CLZ及N-CLZ的血药浓度;并运用逐步回归法分析年龄、性别、CLZ剂量、联用CLNAZ等因素对于CLZ血药浓度的影响。结果:(1)联用CLNAZ可影响CLZ血药浓度和N-CLZ血药浓度(p=0.010,p=0.020);(2)性别、CLZ剂量、联用CLNAZ三因素可影响CLZ血药浓度(p=0.010,p=0.009,p<0.001)。CLZ血药浓度与女性、CLZ剂量呈正相关;与联用CLNAZ呈负相关;(3)CLZ剂量、联用CLNAZ两因素可影响N-CLZ血药浓度(p=0.020,p<0.001)。N-CLZ血药浓度与CLZ剂量呈正相关;与联用CLNAZ呈负相关。结论:联用CLNAZ可对精神分裂症患者的CLZ、N-CLZ血药浓度产生影响;而性别和CLZ剂量等因素对精神分裂症患者的CLZ、N-CLZ血药浓度亦有一定程度的影响。临床上应加强联用氯硝西泮的精神分裂症患者CLZ血药浓度监测,及时调整氯氮平剂量。Background： For patients with schizophrenia clozapine （CLZ） is sometimes co-prescribed with clonazepam （CLNAZ）. However, the impact of administration of CLZ along with CLNAZ on the serum concentration of CLZ and its major metabolite N-CLZ in schizophrenia is not well understood. Aim： To investigate the effects of CLNAZ co-medication, patient gender, age and CLZ dosage on serum concentration of CLZ and norclozapine （N-CLZ） in individuals with schizophrenia. Methods： Serum CLZ and N-CLZ concentrations and demographic data were retrospectively analyzed for 341 patients with schizophrenia. We used SPSS 21.0 to perform stepwise regression to analyze the concentration data and demographics. Variables included in the analysis were： serum concentration of CLZ, N-CLZ, and CLZ dosage, gender, age and CLNAZ co-medication. Results： （1） CLNAZ co-medication significantly affects serum CLZ and N-CLZ concentration in schizophrenics （p=0.010, p=0.020）; （2） CLNAZ co-medication, gender and CLZ dosage significantly affect serum CLZ concentration in patients with schizophrenia （p=O.010, p=0.009, p〈0.001）. Serum CLZ concentration is negatively correlated with CLNAZ co-medication, and is positively correlated with being female and CLZ dosage; （3） CLNAZ co-medication and CLZ dosage were significantly related to serum N-CLZ concentration in participants （p=O.020, p〈0.001）. Serum N-CLZ concentration was negatively correlated with CLNAZ co- medication, and positively correlated with CLZ dosage. Conclusion： CLNAZ co-medication is associated with changes in serum CLZ and N-CLZ concentration. It is indicated that gender and/or CLZ dosage are also related to serum CLZ and N-CLZ concentration. Therapeutic drug monitoring and dosage regulation of CLZ should be performed for patients with schizophrenia who are also taking CLNAZ to maintain a safe and effective serum concentration of CLZ and N-CLZ.

关 键 词：血药浓度 联合用药 氯氮平 去甲氯氮平 氯硝西泮 

分 类 号：R749.3[医药卫生—神经病学与精神病学]