研析奥氮平治疗老年晚期癌症患者抑郁状态的血药浓度与临床疗效关系

Relationship between Serum Concentrations and Clinical Efficacy of Olanzapine in Elder Advanced Cancer Patients with Depression State

目的:研析奥氮平治疗老年晚期癌症患者抑郁状态的血药浓度与临床疗效的关系,促进合理用药。方法:80例这类患者服用2.5 ~ 10 mg·d^-1奥氮平,应用全自动二维液相色谱法(2D-LC/UV)检测患者用药后4周内每周奥氮平血药浓度(C奥氮平);采用汉密尔顿抑郁量表(HAMD-24)于治疗前、治疗后4周内每周评估疗效,应用线性回归方程分析奥氮平剂量与血药浓度相关性,运用Logistic回归和受试者工作曲线(ROC)分析奥氮平血药浓度与临床疗效相关性;采用副反应量表(TESS)评估药物不良反应。结果:奥氮平日剂量(D日)和C奥氮平线性方程呈正相关(r=0.634,P<0.001)。治疗的第1、2、3、4周末,有效组与无效组患者D日、C奥氮平、HAMD-24量表减分率存在显著性差异(P<0.05)。经Logistic回归分析得出年龄大、奥氮平血药浓度低是导致奥氮平治疗效果不理想的影响因素。以C奥氮平作为疗效预测因子绘制治疗第1、2、3、4周末ROC曲线,得出约登指数最大时对应的最佳临界值切点分别11.18、13.89、11.55、12.44 ng·mL^-1;未发现C奥氮平与TESS量表评分相关(P>0.05)。结论:奥氮平血药浓度与日剂量、临床疗效密切相关,治疗老年晚期癌症患者抑郁状态最低有效血药浓度范围为11~14 ng·mL^-1。

Objective:To investigate the relationship between serum concentrations and clinical efficacy of olanzapine in elder advanced cancer patients with depression state.Methods:Eighty elder cancer patients with depression state were treated by olanzapine (2.5^-10 mg·d^-1).The serum concentrations (olanzapine) were monitored by 2D-LC/UV at the end of every week after treatment.The clinical efficacies were evaluated using the Hamilton Depression Scale (HAMD-24) at the baseline and the end of every week after treatment.The side effects were evaluated by the Treatment Emergent Symptom Scale (TESS) at the end of every week after treatment.Analysis of correlation between olanzapine dosages and serum concentrations was done by linear regression.The relationship between serum concentrations and clinical efficacy was investigated using logistic regression and receiver operating characteristic curve (ROC) analysis.Results:The daily doses and the serum concentrations of olanzapine were positively correlated in a linear equation.There were significant differences in ages,daily doses and serum concentrations between the effective group and the ineffective group at the end of 1st,2nd,3rd and 4th week of treatment (P<0.05).Low clinical efficacies were mainly related with high age and low serum concentration.Area under ROC (AUC) of olanzapine concentration (predictor for efficacy) of 4 weeks revealed that the best threshold of response was 11.18,13.89,11.55 and 12.44 ng·mL^-1,respectively,which indicated that the lowest efficacy concentration.The serum concentrations of olanzapine were not correlated with the TESS scores.Conclusions:Clinical efficacy and dosages of olanzapine are associated with its serum concentration closely,and the lowest effective serum concentration range for the treatment of elder advanced cancer patients with depression state was 11^-14 ng·mL^-1.