Chelsea & Westminster Hospital, London, UK.
Department of Infectious Disease, Imperial College London, London, UK.
Clin Pharmacol Ther. 2021 Jul;110(1):64-68. doi: 10.1002/cpt.2099. Epub 2020 Nov 21.
The urgent global public health need presented by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has brought scientists from diverse backgrounds together in an unprecedented international effort to rapidly identify interventions. There is a pressing need to apply clinical pharmacology principles and this has already been recognized by several other groups. However, one area that warrants additional specific consideration relates to plasma and tissue protein binding that broadly influences pharmacokinetics and pharmacodynamics. The principles of free drug theory have been forged and applied across drug development but are not currently being routinely applied for SARS-CoV-2 antiviral drugs. Consideration of protein binding is of critical importance to candidate selection but requires correct interpretation, in a drug-specific manner, to avoid either underinterpretation or overinterpretation of its consequences. This paper represents a consensus from international researchers seeking to apply historical knowledge, which has underpinned highly successful antiviral drug development for other viruses, such as HIV and hepatitis C virus for decades.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）带来的紧迫的全球公共卫生需求促使来自不同背景的科学家们前所未有地汇聚在一起，共同努力快速确定干预措施。迫切需要应用临床药理学原则，这已经得到了其他几个团体的认可。然而，有一个领域值得特别考虑，那就是广泛影响药代动力学和药效学的血浆和组织蛋白结合。游离药物理论的原则已经在药物开发中形成并应用，但目前并未常规应用于 SARS-CoV-2 抗病毒药物。蛋白结合的考虑对于候选药物的选择至关重要，但需要以药物特异性的方式进行正确解释，以避免对其后果的低估或高估。本文代表了国际研究人员的共识，他们试图应用历史知识，这些知识为其他病毒（如 HIV 和丙型肝炎病毒）的抗病毒药物开发提供了数十年的支持。
