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

被引：4

作者：

Dings, Christiane ^{[1
,2
]}

Meiser, Peter ^{[3
]}

Holzer, Frank ^{[3
]}

Flegel, Michael ^{[3
]}

Selzer, Dominik ^{[1
]}

Nagy, Eszter ^{[4
]}

Moesges, Ralph ^{[5
]}

Klussmann, Jens Peter ^{[6
,7
,8
]}

Lehr, Thorsten ^{[1
,2
]}

机构：

[1] Saarland Univ, Dept Clin Pharm, D-66123 Saarbrucken, Germany

[2] Univ Saarland, Saarmetr GmbH, Starterzentrum 1, D-66123 Saarbrucken, Germany

[3] URSAPHARM Arzneimittel GmbH, Ind Str 35, D-66129 Saarbrucken, Germany

[4] CEBINA GmbH, Karl Farkas Gasse 22, A-1030 Vienna, Austria

[5] Univ Cologne, Fac Med, Inst Med Stat & Computat Biol IMSB, Kerpener Str 62, D-50937 Cologne, Germany

[6] Univ Cologne, Fac Med, Ctr Mol Med Cologne CMMC, Robert Koch Str 21, D-50931 Cologne, Germany

[7] Univ Cologne, Fac Med, Dept Otorhinolaryngol, Kerpener Str 62, D-50937 Cologne, Germany

[8] Univ Cologne, Univ Hosp Cologne, Kerpener Str 62, D-50937 Cologne, Germany

来源：

PHARMACEUTICS | 2022年 / 14卷 / 10期

关键词：

COVID-19; SARS-CoV-2; azelastine; PK model; virus kinetic model; HYDROCHLORIDE; ABSORPTION;

D O I：

10.3390/pharmaceutics14102059

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页数：15

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