Human neutrophils show decreased survival upon long-term exposure to clozapine
Human neutrophils show decreased survival upon long-term exposure to clozapine
复制标题
长期接触氯氮平后，人类中性粒细胞的存活率降低
DOI：
10.1002/hup.2629
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Yukihiro Noda
中科院分区：
文献类型：
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作者：
Aya Goto;Akira Yoshimi;Tomoko Nagai;Mako Ukigai;Akihiro Mouri;Norio Ozaki;Yukihiro Noda
氯氮平是一种非典型的抗精神病药物，用于治疗难治性精神分裂症患者，但氯氮平治疗受到严格限制，因为它会引起致命的血液学副作用。我们研究了来自健康受试者的人中性粒细胞短期和长期暴露于氯氮平的影响，并将其与氯氮平，奥氮平和多柔比星的反应性代谢产物的影响进行了比较。（1、10、50或100 μM），氯氮平的反应性代谢产物（50或100 μM）或阿霉素（0.2 μM）并培养短（2 hr）或长（24或48小时）持续时间，结果短期暴露于氯氮平（100 μM）后，人中性粒细胞存活率降低，而在正常对照组中，人中性粒细胞存活率降低。和长期暴露于氯氮平，即使在较低浓度（50 μM）。在氯氮平的反应性代谢产物和长期暴露于阿霉素（0.2 μM）中观察到类似的现象，但奥氮平（1-100 μM）没有观察到类似的现象。我们的研究结果表明，人类中性粒细胞易受氯氮平及其反应性代谢物的浓度和时间依赖性的方式。
ObjectiveClozapine is an atypical antipsychotic prescribed for treatment‐resistant schizophrenic patients, but treatment with clozapine is strictly limited because it can induce lethal‐hematologic side effects. We investigated the effects of short‐ and long‐term exposure of human neutrophils derived from healthy subjects to clozapine and compared them with the effects of reactive metabolite of clozapine, olanzapine, and doxorubicin.MethodsNeutrophils were exposed to clozapine and olanzapine (1, 10, 50, or 100 μM), reactive metabolite of clozapine (50 or 100 μM), or doxorubicin (0.2 μM) and cultured for a short (2 hr) or long (24 or 48 hr) duration, and then the survival rate of neutrophils was calculated.ResultsDecreased human neutrophil survival was observed in short‐term exposure to clozapine (100 μM) and long‐term exposure to clozapine even at a lower concentration (50 μM). A similar phenomenon was observed in reactive metabolite of clozapine and long‐term exposure to doxorubicin (0.2 μM), but not to olanzapine (1–100 μM).ConclusionsThe effect of long‐term exposure to clozapine on neutrophil survival is plausibly associated with delayed onset of agranulocytosis after initial exposure. Our results suggest that human neutrophils are vulnerable to clozapine and its reactive metabolite in a concentration‐ and time‐dependent manner.