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A hyperinflammatory response to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, reminiscent of cytokine release syndrome, has been implicated in the pathophysiology of acute respiratory distress syndrome and organ damage in patients with coronavirus disease 2019 (COVID-19). Agents that inhibit components of the pro-inflammatory cascade have garnered interest as potential treatment options with hopes that dampening the proinflammatory process may improve clinical outcomes. Baricitinib is a reversible Janus-associated kinase (JAK)-inhibitor that interrupts the signaling of multiple cytokines implicated in COVID-19 immunopathology. It may also have antiviral effects by targeting host factors that viruses rely for cell entry and by suppressing type I interferon driven angiotensin-converting-enzyme-2 upregulation. However, baricitinib's immunosuppressive effects may be detrimental during acute viral infections by delaying viral clearance and increasing vulnerability to secondary opportunistic infections. The lack of reliable biomarkers to monitor patients' immune status as illness evolves complicates deployment of immunosuppressive drugs like baricitinib. Furthermore, baricitinib carries the risk of increased thromboembolic events, which is concerning given the proclivity towards a hypercoagulable state in patients with COVID-19. In this article, we review available data on baricitinib with an emphasis on immunosuppressive and antiviral pharmacology, pharmacokinetics, safety, and current progress in COVID-19 clinical trials.

Titel:	Baricitinib: A Review of Pharmacology, Safety, and Emerging Clinical Experience in COVID-19.
Autor/in / Beteiligte Person:	Jorgensen, SCJ ; Tse, CLY ; Burry, L ; Dresser, LD
Link:	Full Text Finder (Volltext)
Zeitschrift:	Pharmacotherapy, Jg. 40 (2020-08-01), Heft 8, S. 843-856
Veröffentlichung:	2012- : Malden, MA : Wiley-Blackwell ; <i>Original Publication</i>: [Carlisle, MA : Pharmacotherapy Publications, c1981-, 2020
Medientyp:	academicJournal
ISSN:	1875-9114 (electronic)
DOI:	10.1002/phar.2438
Schlagwort:	Angiotensin-Converting Enzyme 2 Antiviral Agents pharmacology Antiviral Agents therapeutic use Area Under Curve Azetidines administration & dosage Azetidines adverse effects Betacoronavirus COVID-19 Clinical Trials as Topic Cytokines metabolism Drug Interactions Humans Interferon Type I biosynthesis Metabolic Clearance Rate Pandemics Peptidyl-Dipeptidase A biosynthesis Purines Pyrazoles SARS-CoV-2 Signal Transduction drug effects Sulfonamides administration & dosage Sulfonamides adverse effects Azetidines pharmacology Azetidines therapeutic use Coronavirus Infections complications Inflammation drug therapy Inflammation etiology Janus Kinases antagonists & inhibitors Pneumonia, Viral complications Sulfonamides pharmacology Sulfonamides therapeutic use
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Review Language: English [Pharmacotherapy] 2020 Aug; Vol. 40 (8), pp. 843-856. <i>Date of Electronic Publication: </i>2020 Jul 27. MeSH Terms: Azetidines / pharmacology ; Azetidines / therapeutic use ; Coronavirus Infections / complications ; Inflammation / drug therapy ; Inflammation / etiology ; Janus Kinases / antagonists & inhibitors ; Pneumonia, Viral / complications ; Sulfonamides / pharmacology ; Sulfonamides / *therapeutic use ; Angiotensin-Converting Enzyme 2 ; Antiviral Agents / pharmacology ; Antiviral Agents / therapeutic use ; Area Under Curve ; Azetidines / administration & dosage ; Azetidines / adverse effects ; Betacoronavirus ; COVID-19 ; Clinical Trials as Topic ; Cytokines / metabolism ; Drug Interactions ; Humans ; Interferon Type I / biosynthesis ; Metabolic Clearance Rate ; Pandemics ; Peptidyl-Dipeptidase A / biosynthesis ; Purines ; Pyrazoles ; SARS-CoV-2 ; Signal Transduction / drug effects ; Sulfonamides / administration & dosage ; Sulfonamides / adverse effects References: J Clin Invest. 2020 May 1;130(5):2620-2629. (PMID: 32217835) ; Lancet Infect Dis. 2020 Sep;20(9):1013-1014. 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(PMID: 32444460) Contributed Indexing: Keywords: COVID-19; JAK-inhibitor; Janus-associated kinase inhibitor; SARS-CoV-2; baricitinib; severe acute respiratory syndrome Substance Nomenclature: 0 (Antiviral Agents) ; 0 (Azetidines) ; 0 (Cytokines) ; 0 (Interferon Type I) ; 0 (Purines) ; 0 (Pyrazoles) ; 0 (Sulfonamides) ; EC 2.7.10.2 (Janus Kinases) ; EC 3.4.15.1 (Peptidyl-Dipeptidase A) ; EC 3.4.17.23 (ACE2 protein, human) ; EC 3.4.17.23 (Angiotensin-Converting Enzyme 2) ; ISP4442I3Y (baricitinib) Entry Date(s): Date Created: 20200617 Date Completed: 20200914 Latest Revision: 20220716 Update Code: 20231215 PubMed Central ID: PMC7323235

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Baricitinib: A Review of Pharmacology, Safety, and Emerging Clinical Experience in COVID-19.