Mental Health Research Center, Eastern State Hospital, Lexington, Kentucky.
Psychiatry and Neurosciences Research Group (CTS-549), Institute of Neurosciences, University of Granada, Granada, Spain.
Asia Pac Psychiatry. 2020 Jun;12(2):e12384. doi: 10.1111/appy.12384. Epub 2020 Mar 2.
This narrative review on clozapine blood levels or therapeutic drug monitoring (TDM) includes sections focused on drug clearance and TDM, personalized dosing with TDM, clinical applications of TDM in Asians, and areas needing further study. Asian patients need half the clozapine dose (D) used in the United States to get the same blood concentrations (C). The concentration-to-dose (C/D) ratio measures drug clearance. In the United States, the average clozapine patient usually needs from 300 to 600 mg/day to reach 350 ng/mL. US male smokers reach this therapeutic C with a D of 600 mg/day (C/D ratio of 0.60 = 600/350), whereas US female nonsmokers usually need a D of 300 mg/day (C/D ratio of 1.17 = 300/350). While in the United States, average CLO C/D ratios typically are 0.6-1.2 ng/mL per mg/day, in Asian populations they range from 1.20 in male smokers to 2.40 in female smokers, requiring Ds of 300 to 150 mg/day to obtain 350 ng/mL. Asian patients can become clozapine poor metabolizers (PMs), needing very low Ds (50-150 mg/day) to get therapeutic Cs, by taking inhibitors (fluvoxamine, oral contraceptives and valproic acid), due to obesity, or during inflammations with systemic effects. In 573 Asian patients from five samples, around 1% were PMs due to taking inhibitors, 1% due to inflammation, 1% due to obesity, and 7% were potential genetic PMs. The potential genetic PMs ranged between 3% and 13%, but this prevalence will have to be better established in future studies including genetic testing for possible CYP1A2 mutations, which may explain PM status.
这篇关于氯氮平血药浓度或治疗药物监测（TDM）的叙述性综述包括药物清除和 TDM 、TDM 的个体化给药、TDM 在亚洲人群中的临床应用以及需要进一步研究的领域等部分。亚洲患者需要使用美国氯氮平剂量的一半（D）才能达到相同的血药浓度（C）。浓度-剂量（C/D）比值可衡量药物清除率。在美国，平均氯氮平患者通常需要每天 300 至 600mg 才能达到 350ng/mL。美国男性吸烟者每天服用 600mg 氯氮平（C/D 比值为 0.60=600/350）即可达到这一治疗性 C 值，而美国女性非吸烟者通常需要每天服用 300mg 氯氮平（C/D 比值为 1.17=300/350）。在美国，平均 CLO C/D 比值通常为 0.6-1.2ng/mL/每毫克/天，而在亚洲人群中，其范围从男性吸烟者的 1.20 到女性吸烟者的 2.40，需要每天服用 300 至 150mg 的剂量才能获得 350ng/mL 的血药浓度。亚洲患者可能成为氯氮平弱代谢者（PM），由于服用抑制剂（氟伏沙明、口服避孕药和丙戊酸）、肥胖或全身炎症，需要非常低的剂量（50-150mg/天）才能获得治疗性 C 值。在来自五个样本的 573 名亚洲患者中，约有 1%的患者因服用抑制剂、1%的患者因炎症、1%的患者因肥胖而成为 PM，7%的患者可能是潜在的遗传 PM。潜在的遗传 PM 比例在 3%至 13%之间，但这一患病率在未来的研究中需要进一步证实，包括可能的 CYP1A2 基因突变的基因检测，这可能解释 PM 状态。
