Abstract

1. 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.

2. 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.

3. 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.

4. Colchicine is a narrow therapeutic index drug and dosage regimens tailored to patients’ needs should be designed.

摘要

1. 秋水仙碱被广泛研究用于 COVID-19 患者的心脏保护，因为它可以预防“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，但对于适当的剂量方案尚未达成共识，并且目前使用了多种方案。

2. 在这项研究中，进行了模拟以确定剂量方案在 CVOID-19 患者中达到血浆水平的能力，已知这些剂量方案通常是安全有效的。由于肾脏和肝脏损伤以及药物间相互作用已被确定为增加秋水仙碱毒性的最重要因素，因此在模拟中评估了这些相互作用的影响。

3. 一些剂量方案导致秋水仙碱浓度较高，而另一些则导致低于治疗水平。本研究提出了额外的剂量方案，旨在应用于清除率不足的患者。秋水仙碱每次0.5毫克每天两次给药，可以认为是安全有效的。在清除障碍的情况下，应使用低至 0.25 mg 每日三次或两次的剂量。

4. 秋水仙碱是一种治疗指数窄的药物，应根据患者的需要设计剂量方案。