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Pharmacometric Modeling of the Impact of Azelastine Nasal Spray on SARS-CoV-2 Viral Load and Related Symptoms in COVID-19 Patients

The histamine-1 receptor antagonist azelastine was recently found to impact SARS-CoV-2 viral kinetics in a Phase 2 clinical trial (CARVIN). Thus, we investigated the relationship between intranasal azelastine administrations and viral load, as well as symptom severity in COVID-19 patients and analyz...

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Autores principales: Dings, Christiane, Meiser, Peter, Holzer, Frank, Flegel, Michael, Selzer, Dominik, Nagy, Eszter, Mösges, Ralph, Klussmann, Jens Peter, Lehr, Thorsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609097/
https://www.ncbi.nlm.nih.gov/pubmed/36297492
http://dx.doi.org/10.3390/pharmaceutics14102059
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author Dings, Christiane
Meiser, Peter
Holzer, Frank
Flegel, Michael
Selzer, Dominik
Nagy, Eszter
Mösges, Ralph
Klussmann, Jens Peter
Lehr, Thorsten
author_facet Dings, Christiane
Meiser, Peter
Holzer, Frank
Flegel, Michael
Selzer, Dominik
Nagy, Eszter
Mösges, Ralph
Klussmann, Jens Peter
Lehr, Thorsten
author_sort Dings, Christiane
collection PubMed
description The histamine-1 receptor antagonist azelastine was recently found to impact SARS-CoV-2 viral kinetics in a Phase 2 clinical trial (CARVIN). Thus, we investigated the relationship between intranasal azelastine administrations and viral load, as well as symptom severity in COVID-19 patients and analyzed the impact of covariates using non-linear mixed-effects modeling. For this, we developed a pharmacokinetic (PK) model for the oral and intranasal administration of azelastine. A one-compartment model with parallel absorption after intranasal administration described the PK best, covering both the intranasal and the gastro-intestinal absorption pathways. For virus kinetic and symptoms modeling, viral load and symptom records were gathered from the CARVIN study that included data of 82 COVID-19 patients receiving placebo or intranasal azelastine. The effect of azelastine on viral load was described by a dose–effect model targeting the virus elimination rate. An extension of the model revealed a relationship between COVID-19 symptoms severity and the number of infected cells. The analysis revealed that the intranasal administration of azelastine led to a faster decline in viral load and symptoms severity compared to placebo. Moreover, older patients showed a slower decline in viral load compared to younger patients and male patients experienced higher peak viral loads than females.
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spelling pubmed-96090972022-10-28 Pharmacometric Modeling of the Impact of Azelastine Nasal Spray on SARS-CoV-2 Viral Load and Related Symptoms in COVID-19 Patients Dings, Christiane Meiser, Peter Holzer, Frank Flegel, Michael Selzer, Dominik Nagy, Eszter Mösges, Ralph Klussmann, Jens Peter Lehr, Thorsten Pharmaceutics Article The histamine-1 receptor antagonist azelastine was recently found to impact SARS-CoV-2 viral kinetics in a Phase 2 clinical trial (CARVIN). Thus, we investigated the relationship between intranasal azelastine administrations and viral load, as well as symptom severity in COVID-19 patients and analyzed the impact of covariates using non-linear mixed-effects modeling. For this, we developed a pharmacokinetic (PK) model for the oral and intranasal administration of azelastine. A one-compartment model with parallel absorption after intranasal administration described the PK best, covering both the intranasal and the gastro-intestinal absorption pathways. For virus kinetic and symptoms modeling, viral load and symptom records were gathered from the CARVIN study that included data of 82 COVID-19 patients receiving placebo or intranasal azelastine. The effect of azelastine on viral load was described by a dose–effect model targeting the virus elimination rate. An extension of the model revealed a relationship between COVID-19 symptoms severity and the number of infected cells. The analysis revealed that the intranasal administration of azelastine led to a faster decline in viral load and symptoms severity compared to placebo. Moreover, older patients showed a slower decline in viral load compared to younger patients and male patients experienced higher peak viral loads than females. MDPI 2022-09-27 /pmc/articles/PMC9609097/ /pubmed/36297492 http://dx.doi.org/10.3390/pharmaceutics14102059 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dings, Christiane
Meiser, Peter
Holzer, Frank
Flegel, Michael
Selzer, Dominik
Nagy, Eszter
Mösges, Ralph
Klussmann, Jens Peter
Lehr, Thorsten
Pharmacometric Modeling of the Impact of Azelastine Nasal Spray on SARS-CoV-2 Viral Load and Related Symptoms in COVID-19 Patients
title Pharmacometric Modeling of the Impact of Azelastine Nasal Spray on SARS-CoV-2 Viral Load and Related Symptoms in COVID-19 Patients
title_full Pharmacometric Modeling of the Impact of Azelastine Nasal Spray on SARS-CoV-2 Viral Load and Related Symptoms in COVID-19 Patients
title_fullStr Pharmacometric Modeling of the Impact of Azelastine Nasal Spray on SARS-CoV-2 Viral Load and Related Symptoms in COVID-19 Patients
title_full_unstemmed Pharmacometric Modeling of the Impact of Azelastine Nasal Spray on SARS-CoV-2 Viral Load and Related Symptoms in COVID-19 Patients
title_short Pharmacometric Modeling of the Impact of Azelastine Nasal Spray on SARS-CoV-2 Viral Load and Related Symptoms in COVID-19 Patients
title_sort pharmacometric modeling of the impact of azelastine nasal spray on sars-cov-2 viral load and related symptoms in covid-19 patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609097/
https://www.ncbi.nlm.nih.gov/pubmed/36297492
http://dx.doi.org/10.3390/pharmaceutics14102059
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