A Strategy to Treat COVID-19 Disease with Targeted Delivery of Inhalable Liposomal Hydroxychloroquine: A Non-clinical Pharmacokinetic Study
原文连结:
https://www.biorxiv.org/content/10.1101/2020.07.09.196618v1.full
报告介绍如下，全文请见连结
INTRODUCTION
Hydroxychloroquine (HCQ), an antimalarial and anti-inflammatory drug, is inexpensive, safe, and well tolerated by most patient populations, including those with chronic diseases or immunocompromised status. HCQ is a weak diprotic base that can pass through the lipid cell membrane and preferentially concentrate in acidic cytoplasmic vesicles. HCQ is being studied to prevent and treat coronavirus disease 2019 (COVID-19), possibly via blocking the interactions between virus and angiotensin-converting
enzyme-2 (ACE-2) receptor as well as sialic acids receptor and has shown potential in vitro (1, 2) and preliminary clinical results (3, 4). As of Jul 8, 2020, a total of 232 studies involves HCQ use among 2478 clinical trials for COVID-19 registered with the clinicaltrials.gov.
However, the effective in vivo levels as well as the optimal dosing regimen of HCQ for treating COVID-19 remains unclear. The in vitro EC50 values (0.72 to 17.31 M) proposed for optimized dosing regimens are based on extracellular drug concentration (1, 2). A higher lung (intracellular) concentration to predict the in vivo antiviral efficacy was suggested (5). The HCQ concentration (6.7 g/mL) required to clear 100% of SARS-CoV-2 in vitro might not be achievable with the currently proposed oral
dosing regimen of 800 mg HCQ sulfate orally daily, followed by a maintenance dose of 400 mg given daily for 4 days (2, 6). Further, a high cumulative doses of HCQ may raise concerns of systemic toxicity, including cardiotoxicity (7).
An alternative strategy is needed to bridge the gap between in vitro and clinical use of a potentially effective agent in the context of COVID-19 pandemic. A drug delivery directly to the respiratory tracts while minimizing the systemic exposure is a desirable alternative (5). In this report, a proof-of-concept study was conducted to evaluate the systemic pharmacokinetics (PK) profiles and tissue distribution following a single dose of inhalable liposomal HCQ in a rat model and compared to that of
unformulated HCQ through intravenous (IV) delivery.
看起来是有新的HCQ相关吸入式的新冠肺炎治疗方案，似乎可以降低一般服用的副作用，而且有进行了动物试验，未来不知有没有机会也得到BARDA赞助。而文中也有提到这项新药的厂商是Taiwan Liposome Company，也就是台湾的台微体公司(4152)，去看筹码发现有在公司附近的分点囤了蛮多的货，觉得事有蹊俏，不知可不可以提前布局，等待中文新闻出来应该可以拉一波。想请教生技医疗专业的人怎么解读这份报告，感谢!!!