血清、血浆、红细胞内氯氮平浓度测定的临床意义

目的 探讨精神分裂症病人血清、血浆、红细胞内氯氮平浓度与临床效应的关系。方法 59例精神分裂症病人经氯氮平150～600mg/d治疗8周。采用BPRS,PANSS量表评定临床效应,同时测定血清、血浆、红细胞内氯氮平及它的代谢产物去甲氯氮平浓度。结果 血清、血浆、红细胞内的药物浓度呈两两正相关,未发现血浆及红细胞内药物浓度与疗效指标相关(P值均>0.05);按疗程结束时的BPRS减分率≥30％为有效,分别取血浆氯氮平浓度最低有效阈值100ng/ml、350ng/ml、600ng/ml,相应的有效率56.9％、48％、50％均无显著性差异(χ~2=0.61,P>0.05)。结论 血清、红细胞内氯氮平及去甲氯氮平浓度低于血浆浓度,建议检测血浆浓度;去甲氯氮平在红细胞内分布较多,与临床效应间的关系有待进一步探讨;本研究中氯氮平治疗精神分裂症病人的起效血浆浓度范围很宽,推测患者对药物疗效的反应性是影响血药浓度与临床疗效关系的重要因素,采用氯氮平血药浓度指导临床实践时,应分析是否适用于临床实际情况。

Relationship between Clinical Effects and Concentrations on Serum,Plasma and Red Blood Cell of Clozapine

To study the relationship between clinical effects and concentrations in serum, plasma and red blood cell of clozapine in schizophrenic patients. Methods 59 schizophrenic in - patients was treated by clozapine with the dose range of 150-600 mg/d for 8 weeks. The BPRS.PANSS were used to e-valuate clinical effects. The blood sample were obtained at the same time to measure the concentration of clozapine and its main metabolity N - desmethyclozapine in serum, plasma and red blood cell. Results Serum, plasma concentration were positively correlated with red blood cell concentration. No signifi-cant correlation was found between the clozapine plasma concentration and the change of BPRS. And no sig-nificant correlation was found between the red blood cell clozapine concentration and the change of BPRS, too (P > 0.05); response was defined as a 30% decline in the the total BPRS score from baseline to the end of trial. There is a wide range of plasma clozapine concentration across which individual patients will respond. Conclusions Clozapine and N - desmethyclozapine in plasma should be detected, because serum or red blood cell levels were lower. The norclozapine and clozapine concentration ratio in red blood cell was higher than that in plasma or serum. Its relation with clinical effects need further study, it seems reasonable to state that the antipsychotic effects of clozapine occur over a very broad range of plasma concentration. The defference response of the patients to clozapine was an important factor that effects the threshold concentration. So detect-ing the blood concentration of clozapine in clinical practice, should analyze whether they are fit for the clinical patients or not.