Characteristics of olokizumab pharmacokinetics in patients with novel coronavirus infection COVID-19
- Authors: Tavlueva E.V.1, Zernova E.V.1, Kutepova M.P.1, Kostina N.E.2, Lesina V.S.2, Mould D.R.3, Ito K.3, Zinchenko A.V.4, Dolgorukova A.N.4, Nikolskaya M.V.4, Lemak M.S.4, Filon O.V.4, Samsonov M.Y.4
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Affiliations:
- Inozemtsev Municipal Clinical Hospital
- Voronezh Regional Clinical Hospital No. 1
- Projections Research, Inc
- Joint Stock Company “R-Pharm”
- Issue: Vol 10, No 5 (2022)
- Pages: 460-471
- Section: ORIGINAL ARTICLES
- URL: https://journals.rcsi.science/2307-9266/article/view/252952
- DOI: https://doi.org/10.19163/2307-9266-2022-10-5-460-471
- ID: 252952
Cite item
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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##article.viewOnOriginalSite##About the authors
Evgenia V. Tavlueva
Inozemtsev Municipal Clinical Hospital
Author for correspondence.
Email: tavlev1@mail.ru
ORCID iD: 0000-0002-6796-212X
Doctor of Sciences (Medicine), Leading Researcher of the Department of Pathogenetic Aspects of Aging, Head of the Regional Vascular Center
Russian Federation, 1, Fortunatovskaya St., Moscow, 105187Evgenia V. Zernova
Inozemtsev Municipal Clinical Hospital
Email: evgenya.gor@mail.ru
ORCID iD: 0000-0003-4565-6743
Deputy Chief Physician for Therapeutic Care
Russian Federation, 1, Fortunatovskaya St., Moscow, 105187Marina P. Kutepova
Inozemtsev Municipal Clinical Hospital
Email: kutepovam@mail.ru
ORCID iD: 0000-0002-9283-9721
general practitioner
Russian Federation, 1, Fortunatovskaya St., Moscow, 105187Natalya E. Kostina
Voronezh Regional Clinical Hospital No. 1
Email: nata166k@yahoo.com
ORCID iD: 0000-0002-5128-5005
Head of the Department of Pulmonology
Russian Federation, 151, Moskovsky Ave., Voronezh, 394066Victoria S. Lesina
Voronezh Regional Clinical Hospital No. 1
Email: vita252007@yandex.ru
ORCID iD: 0000-0001-8231-6591
pulmonologist
Russian Federation, 151, Moskovsky Ave., Voronezh, 394066Diane R. Mould
Projections Research, Inc
Email: drmould@pri-home.net
ORCID iD: 0000-0002-8908-0136
PhD, president
United States, 535, Springview Lane, Phoenixville, PA, 19460Kaori Ito
Projections Research, Inc
Email: kaori.ito@appliedpmx.com
PhD-MBA, scientific consultant
United States, 535, Springview Lane, Phoenixville, PA, 19460Arkady V. Zinchenko
Joint Stock Company “R-Pharm”
Email: a.zinchenko@rpharm.ru
ORCID iD: 0000-0001-8148-5086
Head of Biosimilars Research
Russian Federation, Bld. 1, 19, Berzarin St., Moscow, 123154Antonina N. Dolgorukova
Joint Stock Company “R-Pharm”
Email: an.dolgorukova@gmail.com
ORCID iD: 0000-0003-4189-7910
biostatistician
Russian Federation, Bld. 1, 19, Berzarin St., Moscow, 123154Maria V. Nikolskaya
Joint Stock Company “R-Pharm”
Email: mv.nikolskaya@rpharm.ru
ORCID iD: 0000-0001-6716-0357
Head of Medical Records Department
Russian Federation, Bld. 1, 19, Berzarin St., Moscow, 123154Maria S. Lemak
Joint Stock Company “R-Pharm”
Email: lemak@rpharm.ru
ORCID iD: 0000-0003-4793-7477
scientific adviser
Russian Federation, Bld. 1, 19, Berzarin St., Moscow, 123154Olga V. Filon
Joint Stock Company “R-Pharm”
Email: ov.filon@rpharm.ru
ORCID iD: 0000-0002-8735-7429
Director of the Department
Russian Federation, Bld. 1, 19, Berzarin St., Moscow, 123154Mikhail Y. Samsonov
Joint Stock Company “R-Pharm”
Email: samsonov@rpharm.ru
ORCID iD: 0000-0003-2685-1623
Candidate of Sciences (Medicine), Associate Professor, Medical Director
Russian Federation, Bld. 1, 19, Berzarin St., Moscow, 123154References
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