Abstract：
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.
Dividing the trough serum concentration by the dose produces the clozapine C/D ratio. The dose required to reach 350ng/ml was considered the minimum therapeutic dosage and was used to classify patients according to clozapine PM status. Titration speed was assessed.
All 10 patients were possibly clozapine PMs (3 of them had as minimum therapeutic doses: 72, 82 or 83mg/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.
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.
Dividing the trough serum concentration by the dose produces the clozapine C/D ratio. The dose required to reach 350ng/ml was considered the minimum therapeutic dosage and was used to classify patients according to clozapine PM status. Titration speed was assessed.
All 10 patients were possibly clozapine PMs (3 of them had as minimum therapeutic doses: 72, 82 or 83mg/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.
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.
摘要：
背景：氯氮平诱导的心肌炎或任何氯氮平诱导的炎症可能是一种超敏反应，因为滴定对患者的氯氮平代谢而言太快。氯氮平的代谢受祖先的影响,性别,吸烟和肥胖等混杂因素的存在，感染,和抑制剂(例如，丙戊酸盐）导致患者表现为氯氮平代谢不良（PM）。土耳其一家医院发表的一项研究确定了1例氯氮平诱发的胰腺炎和肝炎以及9例氯氮平诱发的心肌炎。为了探索10例患者为氯氮平PMs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：将血清谷浓度除以剂量得出氯氮平C/D比。达到350ng/ml所需的剂量被认为是最小治疗剂量，并用于根据氯氮平PM状态对患者进行分类。评估滴定速度。
结果：所有10例患者可能是氯氮平PMs（其中3例的最低治疗剂量为72、82或83mg/天）。10名患者中的9名可能由于肥胖和/或在滴定期间丙戊酸盐共同处方而表现为氯氮平PM。一个人也有未诊断的感染。在10个病人中,9至少有3个因素中的1个：在第一周或第二周滴定太快，或最终剂量太高。
结论：未来使用氯氮平水平并考虑氯氮平PM状态的作用的研究应探索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。
方法：将血清谷浓度除以剂量得出氯氮平C/D比。达到350ng/ml所需的剂量被认为是最小治疗剂量，并用于根据氯氮平PM状态对患者进行分类。评估滴定速度。
结果：所有10例患者可能是氯氮平PMs（其中3例的最低治疗剂量为72、82或83mg/天）。10名患者中的9名可能由于肥胖和/或在滴定期间丙戊酸盐共同处方而表现为氯氮平PM。一个人也有未诊断的感染。在10个病人中,9至少有3个因素中的1个：在第一周或第二周滴定太快，或最终剂量太高。
结论：未来使用氯氮平水平并考虑氯氮平PM状态的作用的研究应探索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。
