氯氮平的群体药物动力学及其主要代谢物norclozapine中国精神分裂症患者。

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李LJ,商DW,李WB,郭W,王XP,任YP,李,傅PX,霁SM,王陆W, CY

氯氮平的群体药物动力学及其主要代谢物norclozapine中国精神分裂症患者。

学报杂志。2012年11月,33 (11):1409 - 16。doi: 10.1038 / aps.2012.71。Epub 2012年7月23日。

PubMed ID

22820910 (在PubMed

]

文摘

目的:开发一种组合群体药代动力学模型(PPK)的大小和变化来评估暴露于氯氮平及其主要代谢物norclozapine难治性精神分裂症患者在中国通过稀疏采样与关注协变量的影响药代动力学参数。方法:相关病人的浓度数据(如人口数据,药物的历史,给药方案,时间的剂量,采样时间、氯氮平的浓度和norclozapine等)收集使用标准化的数据收集形式。患者的人口学特征,包括性别、年龄、体重、体表面积、吸烟状况、和信息会同时服用以及生化和血液测试结果记录。人每天抽5或更多的香烟在上周被定义为吸烟者。氯氮平的浓度和norclozapine测量使用配有紫外检测器的高效液相色谱系统。使用NONMEM PPK分析。年龄、体重、性别、吸烟状态协变量进行评估为主要。使用规范化的内部模型验证预测分布的错误。结果:共有809个氯氮平浓度数据集和808 norclozapine浓度数据集从162年住院病人(74,88)在多个心理健康网站在中国被包括在内。单舱药代动力学模型与混合误差可能最好的描述氯氮平的浓度时间配置文件和norclozapine。 The population-predicted clearance of clozapine and norclozapine in female nonsmokers were 21.9 and 32.7 L/h, respectively. The population-predicted volumes of distribution for clozapine and norclozapine were 526 and 624 L, respectively. Smoking was significantly associated with increases in the clearance (clozapine by 45%; norclozapine by 54.3%). The clearance was significantly greater in males than in females (clozapine by 20.8%; norclozapine by 24.2%). The clearance of clozapine and norclozapine did not differ significantly between Chinese patients and American patients. CONCLUSION: Smoking and male were significantly associated with a lower exposure to clozapine and norclozapine due to higher clearance. This model can be used in individualized drug dosing and therapeutic drug monitoring.

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药物

氯氮平