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通过检测氯氮平和去甲氯氮平血清浓度，探讨细胞色素Ｐ４５０１Ａ２酶（ＣＹＰ１Ａ２）抑制剂氟伏沙明对体内氯氮平代谢及其去甲基代谢产物生成的影响。９例健康男性志愿者，自身前后对照设计，停药间隔４周，口服单剂氯氮平１０ｍｇ；对照组单服氯氮平，实验组是在氟伏沙明连续９ｄ服用过程中的第４ｄ合用单剂氯氮平。合用氟伏沙明后，导致氯氮平的清除相时点平均浓度增高，去甲氯氮平的早期时点平均浓度降低而后期时点平均浓度增高。合用氟伏沙明前后比较，可见氯氮平的消除半衰期Ｔ１／２、０～２４ｈ药时曲线下面积ＡＵＣ０～２４以及系统清除率Ｃｌｓ的差异有显著意义（Ｐ＜０．０１）。研究结果表明，氟伏沙明显著抑制体内氯氮平的代谢，影响其去甲基代谢产物的生成。ＣＹＰ１Ａ２可能是催化体内氯氮平去甲基代谢的主要代谢酶。
The effects of fluvoxamine, a cytochrome P4501A2 inhibitor (CYP1A2) inhibitor, on the metabolism of clozapine and the production of demethylated metabolites were investigated by measuring the serum concentrations of clozapine and norczolam. 9 healthy male volunteers, before and after their own control design, drug withdrawal interval of 4 weeks, a single oral dose of clozapine 10mg; control group, single-dose clozapine, the experimental group is taking fluvastatin 9d consecutive days 4d Combination of single-dose clozapine. Combined use of fluvoxamine resulted in an increase of mean concentrations of clozapine in the cleared phase, an average decrease of the concentrations of norczapine in the early phase and an increase in the average concentration in the late phase. Before and after the combination of fluvoxamine, the elimination half-life of clozapine was significantly different (P <0.01) between T1 / 2 and 2 ~ 24h and the area under the curve of AUC0 ~ 24 and the systemic clearance rate. The results showed that fluvoxam significantly inhibited clozapine metabolism in vivo, affecting the formation of demethylated metabolites. CYP1A2 may be the main metabolic enzyme that catalyzes the demethylation of clozapine in vivo.