丙戊酸盐、肥胖和其他氯氮平代谢不良的原因在快速滴定的背景下可以解释氯氮平诱导的心肌炎:对土耳其病例系列的重新分析

IF 5.2 3区 医学 Q1 PSYCHIATRY
Aygün Ertuğrul , A. Elif Anıl Yağcıoğlu , Esen Ağaoğlu , Ahmet Alp Karakaşlı , Sertaç Ak , M. Kâzım Yazıcı , Jose de Leon
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引用次数: 11

摘要

氯氮平引起的心肌炎或任何氯氮平引起的炎症都可能是一种超敏反应,因为滴定速度太快,患者的氯氮平代谢跟不上。氯氮平代谢受血统、性别、吸烟和混杂因素(包括肥胖、感染和抑制剂(如丙戊酸))的影响,导致患者表现为氯氮平代谢不良者(PM)。土耳其一家医院发表的一项研究发现了1例氯氮平诱发的胰腺炎和肝炎,9例氯氮平诱发的心肌炎。为了探讨这10例患者是否为氯氮平pm的假设,我们使用浓度剂量比(C/D)调查了他们的血清氯氮平浓度,并仔细审查了他们的滴定法。方法用谷血药浓度除以剂量得到氯氮平C/D比。需要达到350 ng/ml的剂量被认为是最低治疗剂量,并根据氯氮平PM状态对患者进行分类。测定滴定速度。结果10例患者均可能为氯氮平经前综合征,其中3例患者最小治疗剂量分别为72、82、83 mg/d。10例患者中有9例可能表现为氯氮平经前综合症,原因是在滴定期间肥胖和/或丙戊酸共处方。其中一人还患有未确诊的感染。在这10例患者中,9例至少有3个因素中的1个:第一或第二周滴药过快,或最终剂量过高。结论未来使用氯氮平水平并考虑氯氮平PM状态的研究应该探讨是否所有氯氮平诱导的炎症病例都可以通过缺乏个体化滴定来解释。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Valproate, obesity and other causes of clozapine poor metabolism in the context of rapid titration may explain clozapine-induced myocarditis: A re-analysis of a Turkish case series

Introduction

Clozapine-induced myocarditis or any clozapine-induced inflammation may be a hypersensitivity reaction due to titration that was too rapid for the patient's clozapine metabolism. Clozapine metabolism is influenced by ancestry, sex, smoking and the presence of confounders including obesity, infections, and inhibitors (e.g., valproate) causing the patient to behave as a clozapine poor metabolizer (PM). A published study in a Turkish hospital identified 1 case of clozapine-induced pancreatitis and hepatitis and 9 cases of clozapine-induced myocarditis. To explore the hypothesis that the 10 patients were clozapine PMs, their serum clozapine concentrations were investigated using concentration-to-dose (C/D) ratios and their titrations carefully reviewed.

Methods

Dividing the trough serum concentration by the dose produces the clozapine C/D ratio. The dose required to reach 350 ng/ml was considered the minimum therapeutic dosage and was used to classify patients according to clozapine PM status. Titration speed was assessed.

Results

All 10 patients were possibly clozapine PMs (3 of them had as minimum therapeutic doses: 72, 82 or 83 mg/day). Nine of the 10 patients may have behaved as clozapine PMs due to obesity and/or valproate co-prescription during titration. One also had an undiagnosed infection. Of the 10 patients, 9 had at least 1 of 3 factors: too-rapid titration in the first or second weeks, or a final dosage that was too high.

Conclusions

Future studies using clozapine levels and considering the role of clozapine PM status should explore whether or not all cases of clozapine-induced inflammation could be explained by lack of individualized titration.

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来源期刊
自引率
3.30%
发文量
58
期刊介绍: The Spanish Journal of Psychiatry and Mental Health (SJPMH), incorporated into ISSN 1888-9891, is the official scientific publication of the Spanish Society of Psychiatry and Mental Health. The journal focuses on studying mental illnesses, their pathological processes, and their psychosocial consequences, and aims to disseminate scientific advances in all areas related to mental health and illness. SJPMH accepts unpublished works on psychiatry and mental health, including their medical and social implications. The journal provides space for research in the biological, clinical, and psychosocial fields. Manuscripts undergo peer-review by external reviewers before being accepted for publication. SJPMH is indexed in Index Medicus/Medline, IBECS, Social Sciences Citation Index Journal Citation Reports/Social Sciences Edition, and Current Contents/Social and Behavioral Sciences.
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