氯硝西泮治疗睡眠障碍血药浓度和用药剂量、临床疗效及不良反应关系的研究

Effects of Clonazepam Serum Concentrations on Dosage,Pharmacodynamics and ADR in Sleep Disorder Patients

目的 通过研究确定氯硝西泮血药浓度和用药剂量、临床疗效及不良反应之间的关系，确定其有效血药浓度范围，方法 通过对66例服用氯硝西泮治疗的符合《中国精神障碍分类与诊断标准第3版（CCMD-3）》中睡眠障碍诊断标准的病人前瞻性设计，利用HPLC测定其血药浓度，用匹兹堡睡眠质量指数（PSQI）评分和治疗不良反应量表（TESS）分别评价其临床疗效和药物不良反应，并对病人血药浓度与用药剂量、临床疗效及不良反应之间的相关性进行统计学分析。结果 氯硝西泮血药浓度和临床用药剂量之间呈显著正相关（r=0．783，P〈0．01，n=66）。血药浓度与临床疗效之间呈显著正相关（r=0．587，P〈0.01，n=66）。血药浓度与不良反应呈显著正相关（r=0．654，P〈0．01，n=66）．结论 氯硝西泮血药浓度和用药剂量、临床疗效及不良反应之间呈显著相关。推荐氯硝西泮临床治疗血药浓度适宜范围为16-35μg·L^-1，氯硝西泮的血浓度监测对指导个体化合理用药具有临床意义。

OBJECTIVE To investigate the effect of clonazepam concentration on drug doses, clinical effects and side effects in sleep disorder patients.To confirm the effective concentration range in sleep disorder patients treated by clonazepam, METHODS 66 patients with sleep disorders were treated with clonazepam. Clonazepam serum concentrations was determined by HPLC method. Therapeutic efficacy was measured by PSQI and side effect was rated by TESS.The effect of clonazepam serum concentrations on drug doses, clinical effects and side effects was analyzed statistically. RESULTS A significant positive correlation was found between clonazepam serum concentrations and drug doses（ r = 0.783, P 〈 0.01, n = 66）. Clonazepam serum concentrations were significant positive correlated with clinical effects（ r = 0.587, P 〈 0.01, n = 66）. Clonazepam serum concentrations were significant positive correlated with side effects（ r = 0,654, P 〈 0.01, n = 66）. CONCLUSION Clonazepam senum concentrations are significant positive correlated with drug doses, Clonazepam serum concentrations are significant positive correlated with clinical effects, clonazepam serum concentrations are significant positive correlated with side effects.The optimal serum concentrations of clonazepam is 16 - 35μg·L^-1. The results indicate that monitoring clonazepam concentration have the clinical significance for using the drug reasonably.