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Article ; Online: Topical NSAIDs for acute local pain relief:

Pennick, Graham / Robinson-Miller, Adam / Cush, Imogen

Drug development and industrial pharmacy

2021 Volume 47, Issue 6, Page(s) 908–918

Abstract: Objective: The efficacy of topical nonsteroidal anti-inflammatory drugs (NSAIDs) relates not only to the individual NSAID used but also to differences in formulation design. The aim of this study was to investigate the fundamental differences in ... ...

Abstract	Objective: The efficacy of topical nonsteroidal anti-inflammatory drugs (NSAIDs) relates not only to the individual NSAID used but also to differences in formulation design. The aim of this study was to investigate the fundamental differences in ibuprofen and diclofenac drug delivery vehicles, specifically gels and plasters, compared to a recently launched 200 Methods: In vitro Results: Differences were observed in the amount of drug recovered at sacrificial timepoints and rate at which drug was delivered to the target site between plaster and gel formulations of ibuprofen and diclofenac and between plaster formulations of the same drug (ibuprofen). While the amount of drug quantified at sacrificial timepoints did not necessarily determine Conclusions: These findings highlight the importance of intelligent formulation design in determining NSAID delivery through skin layers. Further work is required to quantify drug delivery into deeper tissues and the resultant local anti-inflammatory effects.
MeSH term(s)	Acute Pain/drug therapy ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Diclofenac ; Humans ; Ibuprofen ; Pharmaceutical Preparations ; Skin
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Pharmaceutical Preparations ; Diclofenac (144O8QL0L1) ; Ibuprofen (WK2XYI10QM)
Language	English
Publishing date	2021-06-24
Publishing country	England
Document type	Journal Article
ZDB-ID	751874-2
ISSN	1520-5762 ; 0363-9045
ISSN (online)	1520-5762
ISSN	0363-9045
DOI	10.1080/03639045.2021.1935996
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Article ; Online: Ibuprofen, other NSAIDs and COVID-19: a narrative review.

Laughey, William / Lodhi, Imran / Pennick, Graham / Smart, Lucinda / Sanni, Olutoba / Sandhu, Suneet / Charlesworth, Bruce

Inflammopharmacology

2023 Volume 31, Issue 5, Page(s) 2147–2159

Abstract: At the start of the coronavirus disease 2019 (COVID-19) pandemic (March 2020), there was speculation that non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, used to manage some of the symptoms of COVID-19, could increase the susceptibility ...

Abstract	At the start of the coronavirus disease 2019 (COVID-19) pandemic (March 2020), there was speculation that non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, used to manage some of the symptoms of COVID-19, could increase the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and negatively impact clinical outcomes. In the absence of any robust mechanistic and clinical evidence, this speculation led to confusion about the safety of ibuprofen, contributing to the so-called 'infodemic' surrounding COVID-19. A wealth of evidence has been generated in subsequent years, and this narrative review aims to consider the body of in vitro and in vivo research, observational studies, systematic reviews and meta-analyses on the use of NSAIDs, including ibuprofen, in COVID-19. Overall, the direction of evidence supports that NSAIDs do not increase susceptibility to infection, nor worsen disease outcomes in patients with COVID-19. Neither do they impact the immune response to COVID-19 vaccines. There is no basis to limit the use of NSAIDs, and doing so may deprive patients of effective self-care measures to control symptoms.
MeSH term(s)	Humans ; Ibuprofen/adverse effects ; COVID-19 ; COVID-19 Vaccines ; SARS-CoV-2 ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects
Chemical Substances	Ibuprofen (WK2XYI10QM) ; COVID-19 Vaccines ; Anti-Inflammatory Agents, Non-Steroidal
Language	English
Publishing date	2023-08-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1080058-x
ISSN	1568-5608 ; 0925-4692
ISSN (online)	1568-5608
ISSN	0925-4692
DOI	10.1007/s10787-023-01309-7
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Article ; Online: Analgesia and COVID-19.

Laughey, William F / Lodhi, Imran / Sanni, Olutoba / Pennick, Graham / Charlesworth, Bruce

British journal of clinical pharmacology

2022 Volume 88, Issue 7, Page(s) 3543–3544

MeSH term(s)	Analgesia ; COVID-19 ; Humans ; Pain ; Pain Management ; SARS-CoV-2
Language	English
Publishing date	2022-04-15
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/bcp.15347
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Zs.A 1118: Show issues

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Article ; Online: Ibuprofen, Flurbiprofen, Etoricoxib or Paracetamol Do Not Influence ACE2 Expression and Activity In Vitro or in Mice and Do Not Exacerbate In-Vitro SARS-CoV-2 Infection.

de Bruin, Natasja / Schneider, Ann-Kathrin / Reus, Philipp / Talmon, Sonja / Ciesek, Sandra / Bojkova, Denisa / Cinatl, Jindrich / Lodhi, Imran / Charlesworth, Bruce / Sinclair, Simon / Pennick, Graham / Laughey, William F / Gribbon, Philip / Kannt, Aimo / Schiffmann, Susanne

International journal of molecular sciences

2022 Volume 23, Issue 3

Abstract: SARS-CoV-2 uses the human cell surface protein angiotensin converting enzyme 2 (ACE2) as the receptor by which it gains access into lung and other tissue. Early in the pandemic, there was speculation that a number of commonly used medications-including ... ...

Abstract	SARS-CoV-2 uses the human cell surface protein angiotensin converting enzyme 2 (ACE2) as the receptor by which it gains access into lung and other tissue. Early in the pandemic, there was speculation that a number of commonly used medications-including ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs)-have the potential to upregulate ACE2, thereby possibly facilitating viral entry and increasing the severity of COVID-19. We investigated the influence of the NSAIDS with a range of cyclooxygenase (COX)1 and COX2 selectivity (ibuprofen, flurbiprofen, etoricoxib) and paracetamol on the level of ACE2 mRNA/protein expression and activity as well as their influence on SARS-CoV-2 infection levels in a Caco-2 cell model. We also analysed the ACE2 mRNA/protein levels and activity in lung, heart and aorta in ibuprofen treated mice. The drugs had no effect on ACE2 mRNA/protein expression and activity in the Caco-2 cell model. There was no up-regulation of ACE2 mRNA/protein expression and activity in lung, heart and aorta tissue in ibuprofen-treated mice in comparison to untreated mice. Viral load was significantly reduced by both flurbiprofen and ibuprofen at high concentrations. Ibuprofen, flurbiprofen, etoricoxib and paracetamol demonstrated no effects on ACE2 expression or activity in vitro or in vivo. Higher concentrations of ibuprofen and flurbiprofen reduced SARS-CoV-2 replication in vitro.
MeSH term(s)	Acetaminophen/pharmacology ; Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/metabolism ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; COVID-19/genetics ; COVID-19/metabolism ; COVID-19/pathology ; Caco-2 Cells ; Disease Progression ; Enzyme Activation/drug effects ; Etoricoxib/pharmacology ; Flurbiprofen/pharmacology ; Gene Expression Regulation, Enzymologic/drug effects ; Humans ; Ibuprofen/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; SARS-CoV-2/drug effects ; SARS-CoV-2/physiology ; Virus Internalization/drug effects
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Acetaminophen (362O9ITL9D) ; Flurbiprofen (5GRO578KLP) ; ACE2 protein, human (EC 3.4.17.23) ; Ace2 protein, mouse (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Ibuprofen (WK2XYI10QM) ; Etoricoxib (WRX4NFY03R)
Language	English
Publishing date	2022-01-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23031049
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A narrative review of the potential pharmacological influence and safety of ibuprofen on coronavirus disease 19 (COVID-19), ACE2, and the immune system: a dichotomy of expectation and reality.

Smart, Lucinda / Fawkes, Neil / Goggin, Paul / Pennick, Graham / Rainsford, K D / Charlesworth, Bruce / Shah, Neil

Inflammopharmacology

2020 Volume 28, Issue 5, Page(s) 1141–1152

Abstract: The coronavirus disease 19 (COVID-19) pandemic is currently the most acute healthcare challenge in the world. Despite growing knowledge of the nature of Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), treatment options are still poorly ... ...

Abstract	The coronavirus disease 19 (COVID-19) pandemic is currently the most acute healthcare challenge in the world. Despite growing knowledge of the nature of Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), treatment options are still poorly defined. The safety of non-steroidal anti-inflammatory drugs (NSAIDs), specifically ibuprofen, has been openly questioned without any supporting evidence or clarity over dose, duration, or temporality of administration. This has been further conflicted by the initiation of studies to assess the efficacy of ibuprofen in improving outcomes in severe COVID-19 patients. To clarify the scientific reality, a literature search was conducted alongside considerations of the pharmacological properties of ibuprofen in order to construct this narrative review. The literature suggests that double-blind, placebo-controlled study results must be reported and carefully analysed for safety and efficacy in patients with COVID-19 before any recommendations can be made regarding the use of ibuprofen in such patients. Limited studies have suggested: (i) no direct interactions between ibuprofen and SARS-CoV-2 and (ii) there is no evidence to suggest ibuprofen affects the regulation of angiotensin-converting-enzyme 2 (ACE2), the receptor for COVID-19, in human studies. Furthermore, in vitro studies suggest ibuprofen may facilitate cleavage of ACE2 from the membrane, preventing membrane-dependent viral entry into the cell, the clinical significance of which is uncertain. Additionally, in vitro evidence suggests that inhibition of the transcription factor nuclear factor-κB (NF-kB) by ibuprofen may have a role in reducing excess inflammation or cytokine release in COVID-19 patients. Finally, there is no evidence that ibuprofen will aggravate or increase the chance of infection of COVID-19.
MeSH term(s)	Angiotensin-Converting Enzyme 2 ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/drug therapy ; Humans ; Ibuprofen/adverse effects ; Ibuprofen/therapeutic use ; Inflammation/etiology ; Inflammation/prevention & control ; NF-kappa B/drug effects ; Pandemics ; Peptidyl-Dipeptidase A/drug effects ; Pneumonia, Viral/complications ; Pneumonia, Viral/drug therapy
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; NF-kappa B ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Ibuprofen (WK2XYI10QM)
Keywords	covid19
Language	English
Publishing date	2020-08-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1080058-x
ISSN	1568-5608 ; 0925-4692
ISSN (online)	1568-5608
ISSN	0925-4692
DOI	10.1007/s10787-020-00745-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: A narrative review of the potential pharmacological influence and safety of ibuprofen on coronavirus disease 19 (COVID-19), ACE2, and the immune system: a dichotomy of expectation and reality

Smart, Lucinda / Fawkes, Neil / Goggin, Paul / Pennick, Graham / Rainsford, K D / Charlesworth, Bruce / Shah, Neil

Inflammopharmacology

Abstract	The coronavirus disease 19 (COVID-19) pandemic is currently the most acute healthcare challenge in the world. Despite growing knowledge of the nature of Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), treatment options are still poorly defined. The safety of non-steroidal anti-inflammatory drugs (NSAIDs), specifically ibuprofen, has been openly questioned without any supporting evidence or clarity over dose, duration, or temporality of administration. This has been further conflicted by the initiation of studies to assess the efficacy of ibuprofen in improving outcomes in severe COVID-19 patients. To clarify the scientific reality, a literature search was conducted alongside considerations of the pharmacological properties of ibuprofen in order to construct this narrative review. The literature suggests that double-blind, placebo-controlled study results must be reported and carefully analysed for safety and efficacy in patients with COVID-19 before any recommendations can be made regarding the use of ibuprofen in such patients. Limited studies have suggested: (i) no direct interactions between ibuprofen and SARS-CoV-2 and (ii) there is no evidence to suggest ibuprofen affects the regulation of angiotensin-converting-enzyme 2 (ACE2), the receptor for COVID-19, in human studies. Furthermore, in vitro studies suggest ibuprofen may facilitate cleavage of ACE2 from the membrane, preventing membrane-dependent viral entry into the cell, the clinical significance of which is uncertain. Additionally, in vitro evidence suggests that inhibition of the transcription factor nuclear factor-κB (NF-kB) by ibuprofen may have a role in reducing excess inflammation or cytokine release in COVID-19 patients. Finally, there is no evidence that ibuprofen will aggravate or increase the chance of infection of COVID-19.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #716334
Database	COVID19

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Article ; Online: A narrative review of the potential pharmacological influence and safety of ibuprofen on coronavirus disease 19 (COVID-19), ACE2, and the immune system

Smart, Lucinda / Fawkes, Neil / Goggin, Paul / Pennick, Graham / Rainsford, K.D. / Charlesworth, Bruce / Shah, Neil

a dichotomy of expectation and reality

2020

Abstract	The coronavirus disease 19 (COVID-19) pandemic is currently the most acute healthcare challenge in the world. Despite growing knowledge of the nature of Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), treatment options are still poorly defined. The safety of non-steroidal anti-inflammatory drugs (NSAIDs), specifically ibuprofen, has been openly questioned without any supporting evidence or clarity over dose, duration, or temporality of administration. This has been further conflicted by the initiation of studies to assess the efficacy of ibuprofen in improving outcomes in severe COVID-19 patients. To clarify the scientific reality, a literature search was conducted alongside considerations of the pharmacological properties of ibuprofen in order to construct this narrative review. The literature suggests that double-blind, placebo-controlled study results must be reported and carefully analysed for safety and efficacy in patients with COVID-19 before any recommendations can be made regarding the use of ibuprofen in such patients. Limited studies have suggested: (i) no direct interactions between ibuprofen and SARS-CoV-2 and (ii) there is no evidence to suggest ibuprofen affects the regulation of angiotensin-converting-enzyme 2 (ACE2), the receptor for COVID-19, in human studies. Furthermore, in vitro studies suggest ibuprofen may facilitate cleavage of ACE2 from the membrane, preventing membrane-dependent viral entry into the cell, the clinical significance of which is uncertain. Additionally, in vitro evidence suggests that inhibition of the transcription factor nuclear factor-κB (NF-kB) by ibuprofen may have a role in reducing excess inflammation or cytokine release in COVID-19 patients. Finally, there is no evidence that ibuprofen will aggravate or increase the chance of infection of COVID-19.
Keywords	covid19
Subject code	610
Language	English
Publishing date	2020-08-14
Publisher	Springer Science and Business Media LLC
Publishing country	uk
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A narrative review of the potential pharmacological influence and safety of ibuprofen on coronavirus disease 19 (COVID-19), ACE2, and the immune system

Smart, Lucinda / Fawkes, Neil / Goggin, Paul / Pennick, Graham / Rainsford, K. D. / Charlesworth, Bruce / Shah, Neil

Inflammopharmacology

a dichotomy of expectation and reality

2020 Volume 28, Issue 5, Page(s) 1141–1152

Abstract: Abstract The coronavirus disease 19 (COVID-19) pandemic is currently the most acute healthcare challenge in the world. Despite growing knowledge of the nature of Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), treatment options are still ... ...

Abstract	Abstract The coronavirus disease 19 (COVID-19) pandemic is currently the most acute healthcare challenge in the world. Despite growing knowledge of the nature of Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), treatment options are still poorly defined. The safety of non-steroidal anti-inflammatory drugs (NSAIDs), specifically ibuprofen, has been openly questioned without any supporting evidence or clarity over dose, duration, or temporality of administration. This has been further conflicted by the initiation of studies to assess the efficacy of ibuprofen in improving outcomes in severe COVID-19 patients. To clarify the scientific reality, a literature search was conducted alongside considerations of the pharmacological properties of ibuprofen in order to construct this narrative review. The literature suggests that double-blind, placebo-controlled study results must be reported and carefully analysed for safety and efficacy in patients with COVID-19 before any recommendations can be made regarding the use of ibuprofen in such patients. Limited studies have suggested: (i) no direct interactions between ibuprofen and SARS-CoV-2 and (ii) there is no evidence to suggest ibuprofen affects the regulation of angiotensin-converting-enzyme 2 (ACE2), the receptor for COVID-19, in human studies. Furthermore, in vitro studies suggest ibuprofen may facilitate cleavage of ACE2 from the membrane, preventing membrane-dependent viral entry into the cell, the clinical significance of which is uncertain. Additionally, in vitro evidence suggests that inhibition of the transcription factor nuclear factor-κB (NF-kB) by ibuprofen may have a role in reducing excess inflammation or cytokine release in COVID-19 patients. Finally, there is no evidence that ibuprofen will aggravate or increase the chance of infection of COVID-19.
Keywords	Immunology ; Pharmacology (medical) ; Pharmacology ; covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
ZDB-ID	1080058-x
ISSN	1568-5608 ; 0925-4692
ISSN (online)	1568-5608
ISSN	0925-4692
DOI	10.1007/s10787-020-00745-z
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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