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ＲＰＨＰＬＣ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.
出处
《中国药学杂志》
CAS
CSCD
北大核心
1997年第9期541-544,共4页
Chinese Pharmaceutical Journal
关键词
氯氮平
去甲氯氮平
吸烟
性别
药物动力学
clozapine, norclozapine, pharmacokinetics, smoking, sex, plasma concentration
