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氯喹和羟氯喹的药物基因组学:当前证据和未来意义。

Pharmacogenomics of chloroquine and hydroxychloroquine: current evidence and future implications.

机构信息

Department of Pharmacy, University of Rajshahi, Rajshahi, 6205, Bangladesh.

Division of Pharmacogenomics & Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.

出版信息

Pharmacogenomics. 2023 Oct;24(15):831-840. doi: 10.2217/pgs-2023-0124. Epub 2023 Oct 17.

Abstract

As substrates of CYP2C8, CYP3A4/5 and CYP2D6, chloroquine's (CQ) and hydroxychloroquine's (HCQ) efficacy and safety may be affected by variants in the genes encoding these enzymes. This paper aims to assimilate the current evidence on the pharmacogenomics of CQ/HCQ and to identify risk phenotypes affecting the safety or efficacy of these drugs. It has been found that some , and genetic variants may affect the safety or effectiveness of CQ/HCQ. The phenotypes predictively representing ultra-rapid and poor metabolizers have been considered high-risk phenotypes. After considering these high-risk phenotypes in different ethnic groups, it is predicted that a considerable proportion of patients taking CQ/HCQ may be at risk of either therapeutic failure or severe toxicities.

摘要

作为 CYP2C8、CYP3A4/5 和 CYP2D6 的底物,氯喹(CQ)和羟氯喹(HCQ)的疗效和安全性可能受到编码这些酶的基因变异的影响。本文旨在综合 CQ/HCQ 药物基因组学的现有证据,并确定影响这些药物安全性或疗效的风险表型。已经发现,一些 、 和 遗传变异可能会影响 CQ/HCQ 的安全性或有效性。预测性地表示超快和差代谢者的表型被认为是高风险表型。在考虑了不同种族群体中的这些高风险表型后,预计相当一部分服用 CQ/HCQ 的患者可能面临治疗失败或严重毒性的风险。

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