Colchicine for the treatment of COVID-19 patients: efficacy, safety, and model informed dosage regimens
Colchicine for the treatment of COVID-19 patients: efficacy, safety, and model informed dosage regimens
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DOI：
10.1080/00498254.2021.1909782
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发表时间：
2021-04-12
期刊：
影响因子：
1.8
通讯作者：
Karalis, Vangelis
中科院分区：
文献类型：
--
作者：
Karatza, Eleni;Ismailos, George;Karalis, Vangelis
秋水仙碱被广泛研究用于COVID-19患者的心脏保护，因为它可以防止“细胞因子风暴”现象，并可能减少COVID-19引起的并发症。尽管秋水仙碱具有潜在的有益作用，但对合适的给药方案没有共识，目前使用了许多方案，在这项研究中，进行了模拟以确定给药方案在CVOID-19患者中达到血浆水平的能力，已知其通常是安全有效的。由于肾和肝损害，以及药物相互作用已被确定为最重要的因素增加秋水仙碱的毒性，这些相互作用的影响进行了评估，在simulations.Some剂量方案导致高浓度秋水仙碱，而其他的结果在亚治疗水平。本研究提出了其他剂量方案，旨在应用于清除不足的患者。秋水仙碱每日两次0.5mg给药，可认为安全有效。在清除障碍的情况下，剂量低至0.25毫克，每日三次或每日两次应适用。秋水仙碱是一个狭窄的治疗指数药物和剂量方案应根据患者的需要设计。
Colchicine is widely investigated for cardioprotection of COVID-19 patients since it can prevent the phenomenon of 'cytokine storm' and may reduce the complications arising from COVID-19. Despite the potentially beneficial effects of colchicine, there is no consensus on the appropriate dosage regimen and numerous schemes are currently used.In this study, simulations were performed to identify the ability of dosage regimens to attain plasma levels in CVOID-19 patients, known to be generally safe and efficacious. Since renal and hepatic impairment, as well as, drug-drug interactions have been identified to be the most significant factors increasing colchicine toxicity, the impact of these interactions was assessed in the simulations.Some dosage regimens lead to high colchicine concentrations, while others result in sub-therapeutic levels. Additional dosage schemes were proposed in this study aiming to be applied in patients with clearance insufficiency. Colchicine administration of 0.5 mg twice daily, can be considered safe and effective. In cases of clearance impairment, doses as low as 0.25 mg thrice or twice daily should be applied.Colchicine is a narrow therapeutic index drug and dosage regimens tailored to patients' needs should be designed.