Effect of coadministration of clozapine and fluvoxamine versus clozapine monotherapy on blood cell counts, plasma levels of cytokines and body weight
Effect of coadministration of clozapine and fluvoxamine versus clozapine monotherapy on blood cell counts, plasma levels of cytokines and body weight
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DOI：
10.1007/s002139900351
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发表时间：
2000-04-01
影响因子：
3.4
通讯作者：
Pollmächer, T
中科院分区：
文献类型：
--
作者：
Hinze-Selch, D;Deuschle, M;Pollmächer, T
基本原理：氯氮平治疗与血细胞恶液质和体重增加等副作用有关。细胞因子和可溶性细胞因子受体：瘦素、肿瘤坏死因子-α（TNF-α）、可溶性TNF受体p55和p75以及氯氮平的毒性代谢产物的血浆水平升高被认为是这些副作用的基础。目标.本研究探讨了是否共同管理的选择性氯氮平再摄取抑制剂氟伏沙明，干扰氯氮平的肝脏代谢，影响氯氮平的免疫调节和它的一些副作用。研究方法：以下参数进行了测量：循环水平的细胞因子和可溶性受体，血浆浓度的氯氮平及其代谢产物N-去甲基氯氮平，体重和血细胞计数在11和12精神分裂症住院患者合并和单药治疗，分别在前6周的药物治疗。结果如下：基于氯氮平和N-去甲基氯氮平的血浆水平相当，氟伏沙明联合给药1）减弱和延迟氯氮平诱导的TNF-α血浆水平升高，2）增强和加速氯氮平诱导的瘦素血浆水平升高，对氯氮平诱导的体重增加无显著影响，3）减少粒细胞计数。结论：由于氯氮平、其代谢物N-去甲基氯氮平和氟伏沙明不太可能产生这些差异，其他代谢物可能是原因。氯氮平和氟伏沙明的联合给药提供了进一步研究某些代谢产物、免疫调节和这些副作用之间的假定关联的机会。
Rationale: Clozapine treatment is associated with side-effects such as blood cell dyscrasias and weight gain. Increased plasma levels of the cytokines and soluble cytokine receptors:leptin, tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors p55 and p75, as well as toxic metabolites of clozapine, have been suggested as the basis for these side-effects. Objectives. This study examined whether the coadministration of the selective serotonine reuptake inhibitor fluvoxamine, which interferes with clozapine's hepatic metabolism, affects the immunomodulation by clozapine and some of its side-effects. Methods: The following parameters were measured: circulating levels of the cytokines and soluble receptors, plasma concentrations of clozapine and its metabolite N-desmethylclozapine, body weight and blood cell counts in 11 and 12 schizophrenic inpatients on combined and monotherapy, respectively, before and during the first 6 weeks of medication. Results: On the basis of comparable plasma levels of clozapine and N-desmethylclozapine, the coadministration of fluvoxamine 1) attenuated and delayed the clozapine-induced increase in TNF-alpha plasma levels, 2) enhanced and accelerated the clozapine-induced increase in leptin plasma levels without significant effect on clozapine-induced weight gain, and 3) decreased granulocyte counts. Conclusions: As clozapine, its metabolite N-desmethylclozapine and fluvoxamine are unlikely to make these differences, other metabolites might be responsible. The coadministration of clozapine and fluvoxamine offers the opportunity to investigate further the putative associations between certain metabolites, immunomodulation and these side-effects.