吸烟与性别对氯氮平及去甲氯氮平药动学的影响

 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（t_1／2）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（c_max）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c_max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。

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

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.