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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

Authors :
Christiane Dings
Peter Meiser
Frank Holzer
Michael Flegel
Dominik Selzer
Eszter Nagy
Ralph Mösges
Jens Peter Klussmann
Thorsten Lehr
Source :
Pharmaceutics, Vol 14, Iss 10, p 2059 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

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.

Details

Language :
English
ISSN :
19994923
Volume :
14
Issue :
10
Database :
Directory of Open Access Journals
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
edsdoj.28e32686fe4b9e9a0326145852c1dc
Document Type :
article
Full Text :
https://doi.org/10.3390/pharmaceutics14102059