关键词: 药效学, 氯氮平, 细胞色素P450 1A2, 多态性

Abstract: AIM: To approach the relationship between the metabolism of clozapine in the body of patients with schizophrenia and polymorphisms of -2964 locus in cytochrome P450 1A2 (CYP1A2) for the reasonable use of clozapine. METHODS: A fixed dose administration was applied, HPLC was used for determining drug concentration in blood, and the restriction fragment length polymorphisms (RFLPs) was used for analyzing genotype of CYP1A2. RESULTS: Compared with non-smoking group, the clozapine concentration in plasma of smoking group was lower, while the ratio of desmethylclozapine and clozapine was higher in smoking group (P <0.05 and P <0.01, respectively).The frequency of the allele G in the locus -2964 of CYP1A2 was 0.75, and the frequency of the allele A was 0.25.There was no significant difference between w/w genotype and non-w/w genotype (w/m +m/m) for desmethylclozapine/clozapine in nonsmoking patients (P >0.05), but desmethylclozapine/clozapine of w/w genotype was higher than that of non w/w genotype in smoking patients(P <0.05).Compared with w/w genotype of non-smoking patients, desmethylclozapine/clozapine of w/w genotype of smoking patients was significantly higher (P <0.01), but there was no significant difference for non w/w genotype (P >0.05). CONCLUSION: Smoking can induce the activity of CYP1A2. The inducing ability of the allele locus of CYP1A2 -2964 is stronger at both of G (w/w), and it decreased at G ※A mutation.The polymorphism of CYP1A2 G-2964A is significant to the reasonable use of clozapine in the patients with schizophrenia.

Key words: pharmacodynamics, clozapine, P450 1A2, polymorphism