Short-term celecoxib (celebrex) adjuvant therapy: a clinical trial study on COVID-19 patients

Ghaznavi, Habib; Mohammadghasemipour, Zahra; Shirvaliloo, Milad; Momeni, Mohammad; Metanat, Maliheh; Gorgani, Farzaneh; Abedipour, Fatemeh; Mohammadi, Mahdi; Sartipi, Majid; Khorashad, Ali Reza Salimi; Shahraki, Omolbanin; Ataee, Mohadese; Sheervalilou, Roghayeh; Sargazi, Saman

doi:10.1007/s10787-022-01029-4

Cited by 13 publications

(10 citation statements)

References 47 publications

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“…documented that ibuprofen inhibiting the transcription factor NF‐κB reduces the inflammation and the cytokine storm generated by COVID‐19 and downregulates ACE2 receptors when it is overexpressed during inflammation or viral infection. Ghaznavi et al., 41 recruiting 67 patients with mild–moderate COVID‐19, did not report an impairment of symptoms after the treatment with celecoxib (400 and 200 mg/day) or naproxen (500 mg/day).…”

Section: Methodsmentioning

confidence: 95%

Ibuprofen in the Management of Viral Infections: The Lesson of COVID‐19 for Its Use in a Clinical Setting

Marcianò¹,

Gallelli²,

Rania³

et al. 2023

The Journal of Clinical Pharma

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Nonsteroidal anti‐inflammatory drugs (NSAIDs) are commonly used for the management of fever, pain, and inflammation. However, they have always been considered to have a double‐faced role, according to their capacity to manage inflammation but also their possible reduction of immune system response and diagnosis delay. This last point could favor a dramatic increase of viral infection diffusion, possibly leading to a more severe outcome. The advent of severe acute respiratory syndrome coronavirus 2 excluded the use of NSAIDs, particularly ibuprofen, and then indicated this drug as the better NSAID to manage infected outpatients and prevent complications. Several authors described the role of NSAIDs and ibuprofen in preventing cytokine storm and modulating the immune system. However, the development of both adverse drug reactions (i.e., gastrointestinal, renal, hepatic, and cardiovascular) and drug interaction recalled the necessity of prescribing the better NSAID for each patient. In this narrative review, we describe the role of NSAIDs, particularly of ibuprofen, in the management of viral symptoms, suggesting that the NSAID may be chosen considering the characteristics of the patient, the comorbidity, and the polytherapy.

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Section: Methodsmentioning

confidence: 95%

Ibuprofen in the Management of Viral Infections: The Lesson of COVID‐19 for Its Use in a Clinical Setting

Marcianò¹,

Gallelli²,

Rania³

et al. 2023

The Journal of Clinical Pharma

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“…Samples equivalent to 20 mg CLX were placed in the dissolution medium (500 mL of 0.5% w/v SLS containing distilled water which was maintained at 37 ± 0.5 • C under a stirring rate of 50 rpm). Dissolution tests were performed in triplicate at predetermined time intervals (3,6,10,15,30, and 60 min) for each formulation. The concentrations of the dissolved drug were measured spectrophotometrically (Cecil, UK) at 253 nm, and then the percentages of dissolved CLX were plotted against time.…”

Section: In Vitro Dissolution Studiesmentioning

confidence: 99%

Carrier-Free Inhalable Dry Microparticles of Celecoxib: Use of the Electrospraying Technique

Jahangiri,

Nokhodchi,

Asare-Addo

et al. 2023

Biomedicines

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Upregulation of cyclooxygenase (COX-2) plays an important role in lung cancer pathogenesis. Celecoxib (CLX), a selective COX-2 inhibitor, may have beneficial effects in COVID-19-induced inflammatory storms. The current study aimed to develop carrier-free inhalable CLX microparticles by electrospraying as a dry powder formulation for inhalation (DPI). CLX microparticles were prepared through an electrospraying method using a suitable solvent mixture at two different drug concentrations. The obtained powders were characterized in terms of their morphology, solid state, dissolution behavior, and aerosolization performance. Electrosprayed particles obtained from the ethanol–acetone solvent mixture with a drug concentration of 3 % w/v exhibited the best in vitro aerosolization properties. The value of the fine particle fraction obtained for the engineered drug particles was 12-fold higher than that of the untreated CLX. When the concentration of CLX was increased, a remarkable reduction in FPF was obtained. The smallest median mass aerodynamic diameter was obtained from the electrosprayed CLX at a 3% concentration (2.82 µm) compared to 5% (3.25 µm) and untreated CLX (4.18 µm). DSC and FTIR experiments showed no change in drug crystallinity or structure of the prepared powders during the electrospraying process. The findings of this study suggest that electrospraying has potential applications in the preparation of DPI formulations.

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Section: Drugs Used To Treat Covid-19mentioning

confidence: 99%

“…NSAIDs such as celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, have given a glimmer of hope in COVID-19 therapy by inhibiting viral replication and inflammasomes [ 39 ]. However, celecoxib exhibited cardiovascular toxicity, primarily in patients with autoimmune diseases [ 39 ]. Celecoxib is primarily metabolised by CYP2C9, and patients who lack CYP2C9 activity have an increased exposure to celecoxib and its side effects [ 117 ].…”

Section: Drugs Used To Treat Covid-19mentioning

confidence: 99%

“…Surprisingly, a number of drugs and herbs [ 23 – 28 ] used in COVID-19 therapy are inhibitors [ 29 – 33 ] or inducers of [ 34 , 35 ], or are metabolised by CYP2C9 [ 36 – 39 ]. In addition to the involvement of CYP2C9 in inflammatory processes and cytokine storms during COVID-19 infection, studies regarding CYP2C9 expression and alteration, their mechanism of actions and their impact on COVID-19 pathophysiology and metabolism of therapeutic agents are lacking.…”

Section: Introductionmentioning

confidence: 99%

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Role of Cytochrome P450 2C9 in COVID-19 Treatment: Current Status and Future Directions

Lim

Bishtawi

Lim

2023

Eur J Drug Metab Pharmacokinet

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The major human liver drug metabolising cytochrome P450 (CYP) enzymes are downregulated during inflammation and infectious disease state, especially during coronavirus disease 2019 (COVID-19) infection. The influx of proinflammatory cytokines, known as a ‘cytokine storm’, during severe COVID-19 leads to the downregulation of CYPs and triggers new cytokine release, which further dampens CYP expression. Impaired drug metabolism, along with the inevitable co-administration of drugs or ‘combination therapy’ in patients with COVID-19 with various comorbidities, could cause drug–drug interactions, thus worsening the disease condition. Genetic variability or polymorphism in CYP2C9 across different ethnicities could contribute to COVID-19 susceptibility. A number of drugs used in patients with COVID-19 are inducers or inhibitors of, or are metabolised by, CYP2C9, and co-administration might cause pharmacokinetic and pharmacodynamic interactions. It is also worth mentioning that some of the COVID-19 drug interactions are due to altered activity of other CYPs including CYP3A4. Isoniazid/rifampin for COVID-19 and tuberculosis co-infection; lopinavir/ritonavir and cobicistat/remdesivir combination therapy; or multi-drug therapy including ivermectin, azithromycin, montelukast and acetylsalicylic acid, known as TNR4 therapy, all improved recovery in patients with COVID-19. However, a combination of CYP2C9 inducers, inhibitors or both, and plausibly different CYP isoforms could lead to treatment failure, hepatotoxicity or serious side effects including thromboembolism or bleeding, as observed in the combined use of azithromycin/warfarin. Further, herbs that are CYP2C9 inducers and inhibitors, showed anti-COVID-19 properties, and in silico predictions postulated that phytochemical compounds could inhibit SARS-CoV-2 virus particles. COVID-19 vaccines elicit immune responses that activate cytokine release, which in turn suppresses CYP expression that could be the source of compromised CYP2C9 drug metabolism and the subsequent drug–drug interaction. Future studies are recommended to determine CYP regulation in COVID-19, while recognising the involvement of CYP2C9 and possibly utilising CYP2C9 as a target gene to tackle the ever-mutating SARS-CoV-2.

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Short-term celecoxib (celebrex) adjuvant therapy: a clinical trial study on COVID-19 patients

Cited by 13 publications

References 47 publications

Ibuprofen in the Management of Viral Infections: The Lesson of COVID‐19 for Its Use in a Clinical Setting

Ibuprofen in the Management of Viral Infections: The Lesson of COVID‐19 for Its Use in a Clinical Setting

Carrier-Free Inhalable Dry Microparticles of Celecoxib: Use of the Electrospraying Technique

Role of Cytochrome P450 2C9 in COVID-19 Treatment: Current Status and Future Directions

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