Superior effect of MP‐AzeFlu compared to monotherapy with fluticasone propionate or azelastine on GILZ, MKP‐1 and TTP anti‐inflammatory gene expression in healthy and inflamed upper airway mucosa

Vicens-Artés, Sònia; Roca‐Ferrer, Jordi; Tubita, Valeria; Fuentes, Mireya; Alobid, Isam; Valero, Antonio; Kopietz, Ferdinand; Nguyen, DucTung; Mullol, Joaquim

doi:10.1111/cea.14099

Cited by 3 publications

(2 citation statements)

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“…Anti-inflammatory genes are activated when glucocorticoids (GCs) diffuse across the cell membrane to bind to GC-responsive elements (GREs) on the promoter region of target genes. 11 In previous clinical trials, the combination demonstrated superior efficacy in the treatment of SAR compared with placebo, azelastine HCl, and fluticasone propionate in adults and adolescents in a total of approximately 4000 patients. Other studies have also shown the safety and efficacy of MP-AzeFlu in controlling chronic AR including PAR and vasomotor rhinitis.…”

Section: Introductionmentioning

confidence: 92%

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The Comparative Bioavailability of Fluticasone and Azelastine Delivered as a Single Fixed Dose Combination (MP-AzeFlu) in Comparison to Two Different Formulations of Azelastine and Fluticasone Propionate Following Intranasal Administration in Healthy Chinese Volunteers

Wei¹,

Liu²,

Xue³

et al. 2023

JAA

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Objective Two studies (Study I and Study II) were conducted in healthy Chinese volunteers to confirm that there was no pharmacokinetic drug interaction between AZE and FLU in MP-AzeFlu. The secondary objective was to evaluate the pharmacokinetic parameters of MP-AzeFlu compared with the commercially available mono-components. Methods Both studies were a randomized, open-label, three-period, six-sequence, single-dose cross-over trial (William’s design) conducted at Beijing Hospital (Beijing, China) in September and October of 2019 in 30 healthy adult male and female volunteers. The natural log transformed parameters: AUC 0-tlast , AUC 0-∞ and C max were analyzed. Results The comparison of PK parameters between MP-AzeFlu and Aze (commercially available) showed that the LS mean ratios (90% CI) values for, AUC 0–tlast , AUC 0–∞ and C max were 100.29% (94.31–106.66%), 100.76% (94.60–107.32%) and 93.14% (81.47–106.48%). The comparison of PK parameters between MP-AzeFlu and Flu (commercially available) for the bioavailability evaluation showed that the LS mean ratios (90% CI) values for, AUC 0–tlast , AUC 0–∞ and C max were 83.48% (69.81–99.82%), 100.19% (87.34–114.94%) and 81.91% (68.50–97.95%). Conclusion The study results confirm that neither the FLU or the AZE component in the combination product (MP-AzeFlu), nor the existing qualitative and quantitative differences in the formulation between the currently marketed AZE and FLU mono-product, display significant potential to impact the systemic exposure of AZE or FLU in Chinese subjects.

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Section: Introductionmentioning

confidence: 92%

“…Anti‐inflammatory genes are activated when glucocorticoids (GCs) diffuse across the cell membrane to bind to GC‐responsive elements (GREs) on the promoter region of target genes. 11 …”

Section: Introductionmentioning

confidence: 99%

The Comparative Bioavailability of Fluticasone and Azelastine Delivered as a Single Fixed Dose Combination (MP-AzeFlu) in Comparison to Two Different Formulations of Azelastine and Fluticasone Propionate Following Intranasal Administration in Healthy Chinese Volunteers

Wei¹,

Liu²,

Xue³

et al. 2023

JAA

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Effect of MP‐AzeFlu compared to monotherapy on COX‐2, PGE₂, and EP2 gene expression in upper airway mucosa

Vicens-Artés

Roca‐Ferrer

Tubita

et al. 2022

Immunity Inflam & Disease

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MP‐AzeFlu (intranasal fluticasone and azelastine) has been widely studied and has demonstrated efficacy in Allergic rhinitis with a superior effect compared to these drugs administered individually; however, the mechanism by which MP‐AzeFlu produces this improved clinical effect has not yet been fully explained. In this study, we investigated the effect of MP‐AzeFlu and fluticasone propionate (FP) on arachidonic acid metabolism as measured by changes in regulation of cyclooxygenase (COX) isoforms, prostaglandin (PG) D 2 , PGE 2 , PGE 2 receptor (EP) 2, and EP3. Expression of these key inflammation markers was assessed through an in vitro model of upper airway inflammation using fibroblasts derived from both healthy and inflamed upper airway mucosa. Both MP‐AzeFlu and FP inhibited interleukin‐1β‐induced COX‐2 messenger RNA (mRNA) and protein expression and PGE 2 secretion in vitro. MP‐AzeFlu and FP both upregulated EP2 mRNA expression, though neither upregulated EP2 protein expression. This downregulation of COX‐2 and PGE 2 coupled with upregulation of EP2 receptor expression reinforces the anti‐inflammatory effect of MP‐AzeFlu in upper airway inflammation.

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