COVID-19 Vaccines and the Virus: Impact on Drug Metabolism and Pharmacokinetics

McColl, Eliza R.; Croyle, Maria A.; Zamboni, William C.; Honer, William G.; Heise, Mark T.; Piquette‐Miller, Micheline; Goralski, Kerry B.

doi:10.1124/dmd.122.000934

Cited by 11 publications

(11 citation statements)

References 130 publications

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“…This interaction is extended to drug transporters and other organs which finally exert impact on drug absorption, distribution, metabolism and excretion (ADME), the primary pharmacokinetic clearance pathways for complex formulations (e.g. nanoparticles, biologics) [ 143 ]. For instance, altered ADME of drugs have been observed in Covid-19 infection and vaccination.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, altered ADME of drugs have been observed in Covid-19 infection and vaccination. A clinical case study reported that an increased level of clozapine was observed in an individual with history of oral clozapine treatment over 10 years after receiving mRNA vaccine (Pfizer-BioNTech) for SARS-CoV-2 [ 143 ]. The individual showed symptoms of Covid-9 infection although tested negative repeatedly as well as multiple comorbidities associated with increased risk of neurologic toxicity of clozapine [ 143 ].…”

Section: Discussionmentioning

confidence: 99%

“…A clinical case study reported that an increased level of clozapine was observed in an individual with history of oral clozapine treatment over 10 years after receiving mRNA vaccine (Pfizer-BioNTech) for SARS-CoV-2 [ 143 ]. The individual showed symptoms of Covid-9 infection although tested negative repeatedly as well as multiple comorbidities associated with increased risk of neurologic toxicity of clozapine [ 143 ]. Therefore patients with active viral infection or individuals who have just received vaccination, may have altered innate immune response which in turn impact on the uptake and clearance of drugs.…”

Section: Discussionmentioning

confidence: 99%

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Recent Advances in Inhaled Nanoformulations of Vaccines and Therapeutics Targeting Respiratory Viral Infections

2023

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With the rapid outbreak of respiratory viral infections, various biological (e.g. vaccines, peptides, recombinant proteins, antibodies and genes) and antiviral agents (e.g. ribavirin, palivizumab and valaciclovir) have been successfully developed for the treatment of respiratory virus infections such as influenza, respiratory syncytial virus and SARS-CoV-2 infections. These therapeutics are conventionally delivered via oral, intramuscular or injection route and are associated with several adverse events due to systemic toxicity. The inherent in vivo instability of biological therapeutics may hinder them from being administered without proper formulations. Therefore, we have witnessed a boom in nanotechnology coupled with a needle-free administration approach such as the inhalation route for the delivery of complex therapeutics to treat respiratory infections. This review discussed the recent advances in the inhalation strategies of nanoformulations that target virus respiratory infections.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Recent Advances in Inhaled Nanoformulations of Vaccines and Therapeutics Targeting Respiratory Viral Infections

2023

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“…chemokines and cytokines, and cellular recruitment [ 125 ]. The activated innate immune response generally decreases CYP enzyme activity, and these interactions extend to drug transporters and organs, impacting drug absorption, distribution, metabolism and excretion (ADME) [ 126 ]. Therefore, altered ADME is predicted after SARS-CoV-2 (COVID-19) vaccination [ 126 ].…”

Section: Covid-19 Vaccines: Cyp2c9 Downregulationmentioning

confidence: 99%

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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“…Spike glycoprotein of SARS-CoV-2 is one of the major targets of the host immune system. , Receptor-binding domain (RBD) is immunodominant and accounts for major neutralizing activity in the serum of convalescent COVID-19 patients. , However, spike glycoprotein and RBD both suffer from inherently low immunogenicity and poor pharmacokinetics . Appropriate adjuvant or delivery system is an alternative to enhancing the immune effectiveness of the antigens …”

Section: Introductionmentioning

confidence: 99%

Mucosal SARS-CoV-2 Nanoparticle Vaccine Based on Mucosal Adjuvants and Its Immune Effectiveness by Intranasal Administration

Xiao

Wang

Shen

et al. 2023

ACS Appl. Mater. Interfaces

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SARS-CoV-2 is a respiratory virus that causes significant threats to human health. Mucosal immunity provides a first-line defense to prevent the infection of SARS-CoV-2 in the respiratory tract. Because most SARS-CoV-2 vaccines could not stimulate mucosal immunity in the respiratory tract, appropriate mucosal adjuvants or delivery systems are needed for mucosal vaccine development. Mannan, polyarginine, and 2′,3′-cGAMP are three mucosal adjuvants that could stimulate mucosal immunity. In the present study, the three adjuvants were assembled with a receptor-binding domain (RBD) by electrostatic interaction to generate a nanoparticle vaccine (RBD-MP-cG). RBD-MP-cG elicited mucosal IgA and IgG response in bronchoalveolar lavage and nasal lavage by intranasal administration. It induced a robust RBD-specific antibody response, high levels of protective neutralizing antibody, and ACE2-blocking activity in the mouse sera. It stimulated the splenic secretion of high levels of Th1-, Th2-, and Th17-type cytokines. Thus, RBD-MP-cG elicited strong mucosal immunity and systematic immunity by intranasal administration. RBD-MP-cG was expected to act as a safe, effective, and easily produced mucosal nanoparticle vaccine to combat the infection of SARS-CoV-2.

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COVID-19 Vaccines and the Virus: Impact on Drug Metabolism and Pharmacokinetics

Cited by 11 publications

References 130 publications

Recent Advances in Inhaled Nanoformulations of Vaccines and Therapeutics Targeting Respiratory Viral Infections

Recent Advances in Inhaled Nanoformulations of Vaccines and Therapeutics Targeting Respiratory Viral Infections

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

Mucosal SARS-CoV-2 Nanoparticle Vaccine Based on Mucosal Adjuvants and Its Immune Effectiveness by Intranasal Administration

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