Potential Effects of COVID-19 on Cytochrome P450-Mediated Drug Metabolism and Disposition in Infected Patients.
Potential Effects of COVID-19 on Cytochrome P450-Mediated Drug Metabolism and Disposition in Infected Patients.
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COVID-19对受感染患者的细胞色素P450介导的药物代谢和处置的潜在影响。
DOI：
10.1007/s13318-020-00668-8
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发表时间：
2021-03
影响因子：
1.9
通讯作者：
Arrighi S
中科院分区：
文献类型：
--
作者：
Deb S;Arrighi S
2019年冠状病毒病（COVID-19）自2019年12月首次被发现以来，一直是一场全球健康危机。除了发烧、咳嗽、头痛和呼吸短促外，基于免疫反应的炎症急剧增加是严重急性呼吸综合征冠状病毒（SARS-CoV-2）感染的标志。本文对COVID-19的病理生理学及其对药物代谢和处置的可能影响进行了总结和评论。炎症细胞因子（如白细胞介素、肿瘤坏死因子α）的释放，也被称为“细胞因子风暴”，导致分子病理生理改变，最终导致肺、心脏和肝脏的器官损伤。各种肝功能检查（如丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素、白蛋白）的实验室值表明COVID-19患者可能存在肝细胞损伤。由于肝脏是蛋白质合成的发电站，也是细胞色素P450 （CYP）介导的药物代谢的主要部位，因此即使肝功能状态的微小变化也有可能影响肝脏对外源药物的清除。现在已经确定，细胞因子水平的极端升高在COVID-19患者中很常见，之前对非sars - cov -2病毒感染患者的研究表明，CYP酶可以被感染相关的细胞因子增加和炎症抑制。除了正在研究的COVID-19药物外，患者还可能正在接受治疗合并症的药物；特别是流行病学研究表明，高血压、高血糖和肥胖患者比一般人群更容易感染COVID-19。这使患者的药物-疾病相互作用情况变得复杂，因为研究药物（如瑞德西韦、地塞米松）和合并症药物都可能受到cypp介导的肝脏代谢受损的影响。总之，医疗专业人员必须关注COVID-19和cypp驱动的药物代谢相互作用，以便适当调整剂量或停止使用受影响的药物。
Coronavirus Disease 2019 (COVID-19) has been a global health crisis since it was first identified in December 2019. In addition to fever, cough, headache, and shortness of breath, an intense increase in immune response-based inflammation has been the hallmark of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) virus infection. This narrative review summarizes and critiques pathophysiology of COVID-19 and its plausible effects on drug metabolism and disposition. The release of inflammatory cytokines (e.g., interleukins, tumor necrosis factor α), also known as ‘cytokine storm’, leads to altered molecular pathophysiology and eventually organ damage in the lung, heart, and liver. The laboratory values for various liver function tests (e.g., alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin) have indicated potential hepatocellular injury in COVID-19 patients. Since the liver is the powerhouse of protein synthesis and the primary site of cytochrome P450 (CYP)-mediated drug metabolism, even a minor change in the liver function status has the potential to affect the hepatic clearance of xenobiotics. It has now been well established that extreme increases in cytokine levels are common in COVID-19 patients, and previous studies with patients infected with non-SARS-CoV-2 virus have shown that CYP enzymes can be suppressed by an infection-related cytokine increase and inflammation. Alongside the investigational COVID-19 drugs, the patients may also be on therapeutics for comorbidities; especially epidemiological studies have indicated that individuals with hypertension, hyperglycemia, and obesity are more vulnerable to COVID-19 than the average population. This complicates the drug-disease interaction profile of the patients as both the investigational drugs (e.g., remdesivir, dexamethasone) and the agents for comorbidities can be affected by compromised CYP-mediated hepatic metabolism. Overall, it is imperative that healthcare professionals pay attention to the COVID-19 and CYP-driven drug metabolism interactions with the goal to adjust the dose or discontinue the affected drugs as appropriate.
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