Veys P A, Wilkes S, Shah S, Noyelle R, Hoffbrand A V
Department of Haematology, Royal Free Hospital School of Medicine, London, England.
Drug Saf. 1992;7 Suppl 1:26-32. doi: 10.2165/00002018-199200071-00008.
An incidence of drug-induced neutropenia of 2.5% has been found in the first 1000 patients to be treated with clozapine in the UK. The majority of affected patients experienced mild neutropenia (n = 22) with only 3 patients developing agranulocytosis. Data collected from these 25 patients suggest that the mechanism of neutropenia may be multifactorial. Laboratory investigation using liquid culture systems and immunofluorocytometry has identified clozapine and its major metabolite N-desmethyl clozapine as exhibiting toxic effects against myeloid maturation and myeloid mitotic compartments, respectively. Increased susceptibility to the toxic effects of clozapine was shown in 1 patient who had previously developed clozapine-associated neutropenia. No clinical or laboratory evidence of drug-induced antineutrophil or antimyeloid precursor antibodies was found.
在英国，接受氯氮平治疗的前1000名患者中，药物性中性粒细胞减少症的发生率为2.5%。大多数受影响的患者出现轻度中性粒细胞减少（n = 22），只有3名患者发展为粒细胞缺乏症。从这25名患者收集的数据表明，中性粒细胞减少的机制可能是多因素的。使用液体培养系统和免疫荧光细胞术进行的实验室研究已确定氯氮平及其主要代谢产物N-去甲基氯氮平分别对髓系成熟和髓系有丝分裂区室具有毒性作用。1名先前曾发生氯氮平相关性中性粒细胞减少症的患者对氯氮平的毒性作用表现出更高的易感性。未发现药物诱导的抗中性粒细胞或抗髓系前体抗体的临床或实验室证据。
