吸烟与性别对氯氮平及去甲氯氮平药动学的影响  

The effect of smoking and sex on pharmacokinetics of clozapine and norclozapine

作　　者：彭文兴[1,2] 李焕德[1,2] 许树梧[1,2] 郭兆贵[1,2] 

机构地区：[1]湖南医科大学附属第二医院临床药学研究室 [2]湖南医科大学临床药理国家培训中心

出　　处：《中国药学杂志》1997年第9期541-544,共4页Chinese Pharmaceutical Journal

摘　　要：目的：研究３０例精神分裂症患者服用固定剂量（６ｍｇ·ｋｇ－１）的氯氮平达稳态后的药动学，以及吸烟与性别对药动学的影响。方法：血药浓度采用ＲＰＨＰＬＣ测定，药动学程序进行参数模拟，并用Ｅｐｉｓｔａｔ统计软件包进行ｔ检验。结果：吸烟者氯氮平及其代谢物去甲氯氮平的消除半衰期（ｔ１／２）分别为（９．２２±２．０）ｈ和（８．４±２．７４）ｈ，明显低于非吸烟者［分别为（１３．８９±３．１５）ｈ和（１３．６８±２．３５）ｈ］，峰浓度（ｃｍａｘ）在吸烟者也明显低于非吸烟者［氯氮平：（３０３．９８±１１８．６５）ｎｇ·ｍｌ－１与（５５２．４５±１８６．４１）ｎｇ·ｍｌ－１，去甲氯氮平：（１３３．８５±６２．４２）ｎｇ·ｍｌ－１与（２３０．２±８６．１８）ｎｇ·ｍｌ－１］，女性非吸烟患者的ｃｍａｘ较男性非吸烟患者高，但统计学上差异无显著性。结论：吸烟可加快氯氮平及去甲氯氮平的代谢。OBJECTIVE: To evaluate the influence of smoking and sex on the clinical pharmacokinetics of clozapine and its metabolite norclozapine after oral administration of fix dose (6 mg·kg -1 ) of clozapine to 30 schizophrenic patients (10 smokers, 20 non smokers). METHODS: Plasma levels of clozapine and norclozapine were measured by HPLC. RESULTS: The halflife of elimination (t 1/2 ) was significantly longer in non smokers than that in smokers [clozapine: (13.89±3.15)h vs (9.22±2.0)h; norclozapine: (13.68±2.35)h vs (8.4±2.74)h; P<0.05]. Peak plasma concentrations (c max ) were higher in non smokers than those in smokers [clozapine: (552.45±186.41)ng·ml -1 vs ( 303.98 ±118.65)ng·ml -1 ; norclozapine: (230.20±86.18)ng·ml -1 vs (133.85±62.42)ng·ml -1 ; P<0.05].The plasma c max in female non smokers was higher than that in male non smokers, but no significant difference was noted statistically. CONCLUSION: Smoking accelerates metabolism of clozapine and norclozapine.

关 键 词：氯氮平 去甲氯氮平 吸烟 性别 药物动力学 

分 类 号：R971.4[医药卫生—药品]