利培酮血药浓度与临床效应的关系

Relationship between serum concentration of risperidone and clinical effects

目的:探讨利培酮、9 羟利培酮血清浓度与临床效应的关系。 方法:5 9例精神分裂症患者以利培酮治疗,于第2、4、6周末评定阳性与阴性症状量表(PANSS)、锥体外系副反应量表(RSESE)和静坐不能量表,采用高效液相色谱(HPLC)库仑阵列电化学法测定血药浓度。 结果:9 羟利培酮、活性部分浓度与日剂量存在正相关;血药浓度与PANSS减分率无相关性;出现锥体外系(EPS)反应组的9 羟利培酮、活性部分浓度显著高于未出现组。采用ROC曲线分析,9 羟利培酮浓度2 4 .8μg/ml,活性部分浓度2 6 .1μg/ml可作为预测锥体外系反应的阈浓度。 结论:增加利培酮日剂量会提高血药浓度,但不一定增加疗效;其活性部分的浓度高至一定程度时,出现锥体外系反应的可能性增加。

Objective:To explore the relationship between seru m concentration of risperidone and its 9-hydroxy metabolite (9-hydroxyrisperidon e) and clinical effects in schizophrenic patients. Method:59 sc hizophrenic inpatients were evaluated with PANSS, RSESE and Barnes akathisia sca les at the baseline and at week 2,4,6 after the treatment with risperidone.The b lood samples were obtained at the same time to measure the concentration of risp eridone and 9-hydroxyrisperidone using HPLC electrochemical detection assay. Results:The serum concentrations of 9-hydroxyrisperidone and act ive moiety showed a weak relationship with the oral dose. No significant correla tion was found between serum concentration of risperidone and reduction rate of PANSS.Mean concentration of 9-hydroxyrisperidone and active moiety were signifi cantly higher in patients with extrapyramidal symptoms than those without extrap yramidal symptoms.By the analysis of ROC,24.8 μg/L 9-hydroxyrisperidone and 26 .1 μg/L active moiety could be as threshold concentration to predict extrapyram idal symptoms. Conclusion:The serum levels of risperidone may i ncrease with the increased dosage,but the clinical effects maybe not improve;whe n the concentrations of 9-hydroxyrisperidone and active moiety are higher than threshold concentration,the rate of developing extrapyramidal symptoms may incr ease.