氯氮平的药代动力学及其优化给药方案

THE PHARMACOKINETICS AND OPTIMIZED REGIMEN OF CLOZAPINE

目的：进一步研究氯氮平的药代动力学特征，运用药代动力学参数预测服药的适宜剂量，为临床合理应用氯氮平，防止副反应的发生提供帮助。方法：对住院前至少２周未用过抗精神病药的患者，空腹１２ｈ后ｐｏ５０ｍｇ氯氮平，在给药后测定血药浓度，求得氯氮平的药代动力学参数，按照个体参数计算其服药间隔和服药量，与实际服药间隔和服药剂量进行比较，比较血药浓度与有效浓度范围的差异，提出氯氮平的给药方案。结果：精神分裂症患者氯氮平吸收相的半衰期平均０．５２ｈ，消除相的半衰期平均１７．８３ｈ，清除率为４２Ｌ／ｈ。口服氯氮平吸收较快，平均２ｈ达高峰浓度（０．２６～４．４４ｈ），相同剂量的不同个体达峰浓度差异较大，最低浓度和最高浓度相差８倍多。结论：剂量的调节尽量做到给药个体化。

OBJECTIVE:The aim of the study is to examine the pharmacokinetic feature of clozapine and to optimize its regimen in order to minimize its adverse reactions and promote the rational use of clozapine in clinical practice.METHODS:The study was conducted in 15 patients with schizophrenic disorder for whom no antipsychotic drugs were taken at least within two weeks before hospitalization.They were treated with 50 mg oral dose of clozapine after 12 hours fasting and blood samples were taken after dosing.The pharmacokinetic parameters were calculated from blood drug concentration obtained.An optimized regimen could be obtained by comparing the calculated dose and dosing interval with those of actually used.RESULTS:From this study ,it was revealed that the blood drug concentration varied widely among persons by whom a same dose of clozapine was taken.The difference between the highest and the lowest may be as high as 8 folds.CONCLUSION:For obtaining a safe and effective drug concentration in blood,the dose of clozapine should be individualized.