奥氮平治疗精神分裂症患者的血药浓度参考范围研究

Reference Range of Olanzapine Concentration in Patients with Schizophrenia

目的:研究奥氮平治疗精神分裂症患者的血药浓度参考范围。方法:根据纳入、排除标准,收集2016年6月至2022年3月西安市精神卫生中心住院患者的年龄、性别、日给药剂量、给药时间、日给药次数、联合用药、量表评分以及不良反应。分析奥氮平血药浓度与收集指标的关系。确定奥氮平血药浓度有效参考范围,结合不良反应发生率确定警戒值。结果:不同年龄、日给药剂量患者的奥氮平血药浓度的差异有统计学意义(F=1.138,F=1.322;P<0.05),男性患者显著低于女性[(39.29±24.48)ng/m L vs.(49.93±26.92)ng/m L,Kolmogorov-Smirnov test=0.2014,P<0.01)]。奥氮平血药浓度与日给药剂量比值(r=0.2254,|t|=36.36,P<0.01)、不良反应(|t|=2.013,P<0.05)呈正相关。根据检出率值最大原则,30 ng/m L为参考范围下限值(≥界值检出率为8.561%),90 ng/m L为参考范围上限值(<界值检出率为2.022%),130 ng/m L为警戒值(不良反应发生率≥70%)。下限界值15 ng/m L的检出率优于90 ng/m L(界值检出率:4.187%vs.2.022%)。结论:不同性别、年龄、日给药剂量患者的奥氮平血药浓度存在个体差异,且不良反应发生率均较高,临床应常规监测奥氮平血药浓度。推荐15~90 ng/m L作为参考范围,130 ng/m L作为警戒值。

OBJECTIVE:To study the reference range of olanzapine concentration in the treatment of schizophrenia.METHODS:According to inclusion and exclusion criteria,age,gender,daily dose,administration time,daily administration frequency,drug combination,scale score and adverse drug reactions of inpatients from Xi’an Mental Health Center from Jun.2016 to Mar.2022 were collected.The correlation between olanzapine concentration and collection index was analyzed.The effective reference range of olanzapine concentration was determined,and the warning value was determined combined with the incidence of adverse drug reactions.RESULTS:There were statistically significant differences in olanzapine concentration among patients with different ages and daily doses(F=1.138,F=1.322;P<0.05),the olanzapine concentration of male patients was significantly lower than that of female patients[(39.29±24.48)ng/mL vs.(49.93±26.92)ng/mL,Kolmogorov-Smirnov test=0.2014,P<0.01)].Olanzapine concentration was positively correlated with daily dose ratio(r=0.2254,t=36.36,P<0.01),adverse drug reactions(t=2.013,P<0.05).According to the principle of maximum detection rate value,30 ng/mL was the lower limit of the reference range(≥threshold detection rate was 8.561%),90 ng/mL was the upper limit of the reference range(<threshold detection rate was 2.022%),130 ng/mL was the alert value(adverse drug reaction rate≥70%).The detection rate of 15 ng/mL was better than 90 ng/mL(threshold detection rate:4.187%vs.2.022%).CONCLUSIONS:There are individual differences in patients using olanzapine with different gender,age and daily dose,and the incidence of adverse drug reactions is high,so that olanzapine concentration should be routinely monitored clinically.It is recommended that 15 to 90 ng/mL be used as the reference range and 130 ng/mL as the alert value.