CHARACTERISTICS OF OLOKIZUMAB PHARMACOKINETICS IN PATIENTS WITH NOVEL CORONAVIRUS INFECTION COVID-19

E. V. Tavlueva, E. V. Zernova, M. P. Kutepova, N. Kostina, V. Lesina, D. Mould, K Ito, A. V. Zinchenko, A. Dolgorukova, M. V. Nikolskaya, M. Lemak, O. Filon, M. Samsonov
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Abstract

The aim of the article is to study pharmacokinetic characteristics of intravenous olokizumab in patients with moderate COVID-19 to relieve a hyperinflammation syndrome.Materials and methods. The pharmacokinetic study was conducted as a part of a phase III clinical study (RESET, NCT05187793) on the efficacy and safety of a new olokizumab regimen (intravenous, at the doses of 128 mg or 256 mg) in COVID-19 patients. Plasma concentrations of olokizumab were determined by the enzyme immunoassay. The population analysis was performed using a previously developed pharmacokinetic model based on a linear two compartment.Results. The pharmacokinetic analysis included the data from 8 moderate COVID-19 patients who had been administrated with olokizumab intravenously at the dose of 128 mg. According to the analysis results in this population, there was an increase in the drug clearance, compared with the data obtained in healthy volunteers and the patients with rheumatoid arthritis: 0.435, 0.178 and 0.147 l/day, respectively. The parameters analysis within the framework of a population pharmacokinetic model showed that the main factors for the increased olokizumab clearance are a high body mass index. In addition, the presence of COVID-19 itself is an independent factor in increasing the drug clearance.Conclusion. After the intravenous olokizumab administration, an increase in the drug clearance is observed in moderate COVID-19 patients against the background of the disease course. The main contribution to the increased clearance is made by the characteristics of the population of COVID-19 patients associated with the risk of a severe disease and inflammation. When administered intravenously at the dose of 128 mg, a therapeutically significant olokizumab level was maintained throughout the acute disease phase for 28 days.
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新型冠状病毒感染COVID-19患者olokizumab药代动力学特征
本文的目的是研究中度COVID-19患者静脉注射olokizumab的药代动力学特征,以缓解过度炎症综合征。材料和方法。该药代动力学研究是作为III期临床研究(RESET, NCT05187793)的一部分进行的,该研究旨在研究新olokizumab方案(静脉注射,剂量为128 mg或256 mg)在COVID-19患者中的有效性和安全性。采用酶免疫分析法测定olokizumab的血药浓度。群体分析使用先前开发的基于线性双区室的药代动力学模型进行。药代动力学分析包括8名中度COVID-19患者的数据,这些患者静脉注射了128 mg的olokizumab。根据该人群的分析结果,与健康志愿者和类风湿关节炎患者的数据相比,药物清除率分别增加了0.435、0.178和0.147 l/天。在人群药代动力学模型框架内的参数分析显示,olokizumab清除率增加的主要因素是高体重指数。此外,COVID-19本身的存在是提高药物清除率的一个独立因素。静脉注射olokizumab后,在疾病病程背景下,观察到中度COVID-19患者的药物清除率增加。清除率增加的主要原因是COVID-19患者群体与严重疾病和炎症风险相关的特征。当以128mg的剂量静脉给药时,在整个急性疾病期维持治疗显著的olokizumab水平28天。
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