Introduction

In December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began, resulting in a number of antivirals and immune modulators being repurposed to treat the associated coronavirus disease 2019 (COVID-19). Many patients requiring treatment for COVID-19 may have either pre-existing renal or hepatic disease or experience acute renal/hepatic injury as a result of the acute infection. Altered renal or hepatic function can significantly affect drug concentrations of medications due to impaired drug metabolism and excretion, resulting in toxicity or reduced efficacy. The aim of this paper is to review the pharmacokinetics and available study data for the experimental COVID-19 therapies in patients with any degree of renal or hepatic impairment to make recommendations for dosing.

Methods

COVID-19 agents included in these recommendations were listed as primaries on the University of Liverpool COVID-19 drug interaction website (www.covid19-druginteractions.org), initially identified from Clinicialtrials.gov and ChicCTR.org.cn. A literature search was performed using PubMed and EMBASE as well as product licences and pharmacokinetic databases.

Findings

Remdesivir, dexamethasone, azithromycin, favipiravir, lopinavir/ritonavir, atazanavir, hydroxychloroquine, interferon beta, ribavirin, tocilizumab, anakinra and sarilumab were identified as experimental drugs being used in COVID-19 trials as of November 2020. Limited study data was found for these drugs in patients with renal or hepatic impairment for COVID-19 or other indications. Recommendations were made based on available data, consideration of pharmacokinetic properties (including variability), the dosing and anticipated treatment duration of each regimen in COVID-19 and known toxicities.

Conclusion

Dosing of drugs used to treat COVID-19 in patients with renal or hepatic impairment is complex. These recommendations were produced to provide guidance to clinicians worldwide who are treating patients with COVID-19, many of whom will have some degree of acute or chronic renal or hepatic impairment.

中文翻译：

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肾损伤和肝损伤患者重新调整用途的 COVID-19 药物剂量建议

介绍

2019 年 12 月，新型严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 开始爆发，导致许多抗病毒药物和免疫调节剂被重新用于治疗相关的 2019 冠状病毒病 (COVID-19)。许多需要治疗 COVID-19 的患者可能已有肾脏或肝脏疾病，或因急性感染而出现急性肾/肝损伤。由于药物代谢和排泄受损，肾或肝功能改变可显着影响药物浓度，导致毒性或疗效降低。本文的目的是回顾实验性 COVID-19 疗法在任何程度的肾功能或肝功能损害患者中的药代动力学和可用研究数据，以提出剂量建议。

方法

这些建议中包含的 COVID-19 药物在利物浦大学 COVID-19 药物相互作用网站 (www.covid19-druginteractions.org) 上被列为初选药物，最初是从 ClinicalTrials.gov 和 ChicCTR.org.cn 确定的。使用 PubMed 和 EMBASE 以及产品许可证和药代动力学数据库进行文献检索。

发现

截至 2020 年 11 月，瑞德西韦、地塞米松、阿奇霉素、法匹拉韦、洛匹那韦/利托那韦、阿扎那韦、羟氯喹、干扰素 β、利巴韦林、托珠单抗、阿那白滞素和 sarilumab 被确定为用于 COVID-19 试验的实验药物。这些药物的研究数据有限。患有肾功能或肝功能损害的患者用于治疗 COVID-19 或其他适应症的药物。建议是根据现有数据、药代动力学特性（包括变异性）、COVID-19 每种方案的剂量和预期治疗持续时间以及已知毒性的考虑而提出的。

结论

用于治疗肾功能或肝功能不全患者的 COVID-19 的药物剂量很复杂。这些建议旨在为全世界治疗 COVID-19 患者的临床医生提供指导，其中许多患者患有某种程度的急性或慢性肾功能或肝功能损害。