精神障碍症患者氯氮平血药浓度监测结果及影响因素分析

Monitoring results and influencing factors of clozapine plasma concentration in patients with mental disorders

目的分析精神障碍症患者口服氯氮平后血药浓度的影响因素,为个体化治疗提供参考。方法回顾性分析2021年1月至10月在安徽医科大学附属巢湖医院药剂科治疗药物监测实验室(TDM)进行氯氮平血药浓度监测的221例住院患者报告,收集患者性别、年龄、BMI、吸烟史、氯氮平剂量、联合用药情况和血药浓度监测结果等信息,并采用单因素方差分析和二元logistic回归分析精神障碍症患者氯氮平血药浓度监测结果及其影响因素。结果221例监测报告中,氯氮平血药浓度在有效血药浓度范围(350~600 ng/ml)内74例(正常浓度组),低于有效血药浓度范围(<350 ng/ml)103例(低浓度组),超过有效血药浓度范围(>600 ng/ml)44例(高浓度组)。单因素方差分析结果显示,不同氯氮平血药浓度组患者的氯氮平日服药剂量、标准剂量、吸烟史、病程、肝功能异常差异有统计学有意义(均P<0.05)。221例患者与氯氮平联合使用最多的抗精神病药物依次为丙戊酸钠、氨磺必利、阿立哌唑和碳酸锂。正常浓度组使用氯氮平联合≥2种抗精神类药物比例高于低浓度组和高浓度组,差异有统计学意义(均P<0.05)。二元logistic回归分析结果显示,联合使用1种抗精神病药物和≥2种抗精神病药物可能有助于精神障碍症患者氯氮平血药浓度达到目标浓度(350~600 ng/ml),其中联合两种药物更有益[OR(95%CI):1.795(0.753~4.282)],差异有统计学意义(P<0.05)。结论氯氮平血药浓度个体间差异大,治疗窗窄,需结合患者的基本信息和临床信息等因素调整给药剂量,定期监测血药浓度,从而达到个体化用药的安全有效。

Objective To analyze the influencing factors of clozapine plasma concentration in patients with mental disorders after oral administration,so as to provide reference for individualized treatment.Methods Retrospective analysis was made on 221 inpatient reports of Clozapine blood concentration monitoring in the Therapeutic Drug Monitoring Laboratory(TDM)of the Pharmacy Department of the Chaohu Hospital Affiliated to Anhui Medical University from January to October 2021,and information such as patient gender,age,body mass index(BMI),smoking history,clozapine dose,combined drug use and blood concentration monitoring results were collected;Single factor analysis of variance and binary logistic regression were used to analyze the monitoring results of clozapine blood concentration in patients with mental disorders and its influencing factors.Results Among 221 monitoring reports,74 cases(normal concentration group)had clozapine plasma concentration within the effective plasma concentration range(350-600 ng/ml),103 cases(low concentration group)were lower than the effective plasma concentration range(<350 ng/ml),and 44 cases(high concentration group)were higher than the effective plasma concentration range(>600 ng/ml).The results of single factor analysis of variance showed that there were statistically significant differences in daily dose of clozapine,standard dose,smoking history,course of disease,and abnormal liver function of patients in different blood concentration groups of clozapine(all P<0.05).The most frequently used antipsychotic drugs in 221 patients with clozapine were sodium valproate,amisulpride,aripiprazole and lithium carbonate in turn.The proportion of clozapine combined with≥2 antipsychotics in the normal concentration group was higher than that in the low concentration group and the high concentration group,and the difference was statistically significant(P<0.05).The results of binary logistic regression analysis showed that the combination of one antipsychotic drug and≥two antipsychotic drugs might help the blood concentration of clozapine in patients with mental disorders reach the target concentration(350-600 ng/ml),and the combination of two drugs was more beneficial[OR(95%CI):1.795(0.753-4.282)],with a statistically significant difference(P<0.05).Conclusions Clozapine plasma concentration varies greatly among individuals,and the therapeutic window is narrow.It is necessary to adjust the dosage in combination with the basic information and clinical information of patients,and regularly monitor the plasma concentration,so as to achieve the safety and effectiveness of individualized drug use.