Netherlands Pharmacovigilance Centre Lareb, Hertogenbosch, the Netherlands.
Unit of PharmacoTherapy, Epidemiology & -Economics, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands.
Br J Clin Pharmacol. 2022 Feb;88(2):853-857. doi: 10.1111/bcp.14992. Epub 2021 Aug 5.
The antipsychotic drug clozapine is associated with weight gain. The proposed mechanisms include blocking of serotonin (5-HT ), dopamine (D ) and histamine (H ) receptors. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2) to norclozapine, a metabolite with more 5-HT -receptor and less H blocking capacity. We hypothesized that norclozapine serum levels correlate with body mass index (BMI), waist circumference and other parameters of the metabolic syndrome. We performed a retrospective cross-sectional study in 39 patients (female n = 8 (20.5%), smokers n = 18 (46.2%), average age 45.8 ± 9.9 years) of a clozapine outpatient clinic in the Netherlands between 1 January 2017 and 1 July 2020. Norclozapine concentrations correlated with waist circumference (r = 0.354, P = .03) and hemoglobin A1c (HbA1c) (r = 0.34, P = .03). In smokers (smoking induces CYP1A2), norclozapine concentrations correlated with waist circumference (r = 0.723, P = .001), HbA1c (r = 0.49, P = .04) and BMI (r = 0.63, P = .004). Elucidating the relationship between norclozapine and adverse effects of clozapine use offers perspectives for interventions and treatment options.
抗精神病药物氯氮平与体重增加有关。提出的机制包括阻断 5-羟色胺（5-HT）、多巴胺（D）和组胺（H）受体。氯氮平被细胞色素 P450 1A2（CYP1A2）代谢为去氯氮平，一种具有更多 5-HT 受体和更少 H 阻断能力的代谢物。我们假设去氯氮平血清水平与体重指数（BMI）、腰围和代谢综合征的其他参数相关。我们在荷兰的一个氯氮平门诊进行了一项回顾性横断面研究，纳入了 2017 年 1 月 1 日至 2020 年 7 月 1 日期间的 39 名患者（女性 n=8（20.5%），吸烟者 n=18（46.2%），平均年龄 45.8±9.9 岁）。去氯氮平浓度与腰围（r=0.354，P=0.03）和血红蛋白 A1c（HbA1c）（r=0.34，P=0.03）相关。在吸烟者中（吸烟诱导 CYP1A2），去氯氮平浓度与腰围（r=0.723，P=0.001）、HbA1c（r=0.49，P=0.04）和 BMI（r=0.63，P=0.004）相关。阐明去氯氮平与氯氮平使用不良影响之间的关系为干预和治疗选择提供了新视角。
