精神分裂症患者氯氮平治疗的血浆、红细胞内浓度与临床效应关系的初步探讨

Relationship between Clinical Effects and Clozapine Concentrations in Plasma andRed Blood Cell in Schizophrenia

目的:探讨氯氮平治疗精神分裂症的血浆、红细胞内浓度与临床效应的关系.方法:59例符合<国际疾病分类>第10版(ICD-10)精神分裂症诊断标准的病人,氯氮平150～600mg·d-1治疗8周.采用常用量表评定临床效应,同时测定血浆、红细胞内氯氮平和去甲氯氮平浓度.结果:①血浆、红细胞之间的氯氮平及其代谢物浓度呈正相关(P<0.001),氯氮平、去甲氯氮平红细胞/血浆浓度比值分别为26.7%±5.5%、50.5%±10.5%.②血浆、红细胞内氯氮平浓度与疗效和药物不良反应指标均不相关(P>0.05).③利用受试者工作曲线(ROC)未能找出血浆和红细胞内最低有效阈浓度(受试者工作曲线下面积均<0.5,P>0.05).④有效组在入组前简明精神病评定量表(BPRS)总分和思维障碍因子分、阳性和阴性症状量表(PANSS)一般情况量表分方面显著高于无效组(P<0.05).结论:①氯氮平及其代谢产物在红细胞内浓度与血浆浓度相关良好,比例稳定.②血浆和红细胞内氯氮平最低有效阈浓度未能找到,患者对氯氮平的疗效是影响阈浓度值的重要因素.

OBJECTIVE:TO study the relationship between clinical effects andclozapine concentrations in plasma,red blood cell in schizophrenia treated byclozapine. METHODS:59 inpatients who met the ICD-l0 criteria for schizophreniawas treated by clozapine of a dose range of l50-600 mg.d-1 for 8 weeks. Clinicaleffects was evaluated by the general scales. The blood samples were obtained atthe same time to measure clozapine and N-desmethylclozapine concentration inplasma and red blood cell. RESULTS:(l) Plasma clozapine concentration weresignificantly positive correlated with red blood cell concentration(P<0.00l). Themean RBC/plasma concentration ratios were 26.7%±5.5%,50.5%±l0.5% forclozapine and N-desmethylclozapine, respectively. (2) No significant correlationwas found between plasma or red blood cell clozapine concentration and clinicalcurative effects or side effects(P<0.05). (3) Through use of a receiver operator curvethe threshold plasma or red blood cell clozapine concentration were not found ROC area<0.5, P<0.05). (4) The responders had significantly higher scores of BPRStotal, the thought disturbances factor of BPRS and the general PANSS subscalethan that of the nonresponders (P<0.05). CONCLUSON:(l) Clozapine red bloodcell concentration were significantly positive correlated with the plasmaconcentration and the RBC/plasma concentration ratios were fixed. (2) The thresholdplasma or red blood cell clozapine concentration were not found. The difference of response of the patients to clozapine wasan important factor that affects the threshold concentration.