Universität zu Köln

Dings, Christiane, Meiser, Peter ORCID: 0000-0002-6689-0056, Holzer, Frank, Flegel, Michael, Selzer, Dominik, Nagy, Eszter, Moesges, Ralph, Klussmann, Jens Peter ORCID: 0000-0002-8223-7954 and Lehr, Thorsten ORCID: 0000-0002-8372-1465 (2022). Pharmacometric Modeling of the Impact of Azelastine Nasal Spray on SARS-CoV-2 Viral Load and Related Symptoms in COVID-19 Patients. Pharmaceutics, 14 (10). BASEL: MDPI. ISSN 1999-4923

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dings, Christiane UNSPECIFIED UNSPECIFIED UNSPECIFIED Meiser, Peter UNSPECIFIED orcid.org/0000-0002-6689-0056 UNSPECIFIED Holzer, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Flegel, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Selzer, Dominik UNSPECIFIED UNSPECIFIED UNSPECIFIED Nagy, Eszter UNSPECIFIED UNSPECIFIED UNSPECIFIED Moesges, Ralph UNSPECIFIED UNSPECIFIED UNSPECIFIED Klussmann, Jens Peter UNSPECIFIED orcid.org/0000-0002-8223-7954 UNSPECIFIED Lehr, Thorsten UNSPECIFIED orcid.org/0000-0002-8372-1465 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-675614
DOI:	10.3390/pharmaceutics14102059
Journal or Publication Title:	Pharmaceutics
Volume:	14
Number:	10
Date:	2022
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1999-4923
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HYDROCHLORIDE; ABSORPTION Multiple languages Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67561