The treatment of drug-induced rhinitis with an original intranasal combination: Efficacy and safety in experimental animals

Abstract

Rhinitis medicamentosa (RM) is a common complication of prolonged use of nasal decongestants, leading to structural changes in the nasal mucosa. Despite the effectiveness of intranasal glucocorticosteroids, their use may be accompanied by side effects.Tha aim. To investigate the efficacy and safety of the original combined intranasal therapy consisting of mometasone furoate and dexpanthenol as the main active ingredients in experimental animals.Materials and methods. An efficacy research was conducted on 18 Chinchilla Soviet rabbits: 3 individuals without RM (control) and 15 individuals with induced RM. The model of induced RM was confirmed by histological examination of the nasal mucosa of 3 randomly selected out of 15 animals after necropsy. The remaining 12 rabbits with RM were divided into 4 groups (n=3): untreated, as well as those with induced RM without treatment, those treated with 5% dexpanthenol, those treated with 0.05% mometasone furoate, and those receiving combination therapy with the two above drugs. RM was induced by administration of 0.1% xylometazoline for 14 days. The safety assessment experiment was conducted on 80 outbred rats (4 groups of 10 females and 10 males each: 3 groups with combined therapy at doses of 50, 200 and 800 µl, respectively, and 4 group (control) with saline) with 28-day intranasal administration. To assess the effectiveness, histological analysis (assessment of structural changes in the nasal mucosa) and photoplethysmography (assessment of the microcirculation of the nasal cavity by cold sampling) were used. To assess the safety of combination therapy, the clinical condition of animals, hematological and biochemical studies, assessment of the hemostasis system, and histological analysis of internal organs were performed. Results. The histological examination revealed pronounced dystrophic changes in the nasal mucosa in animals with induced MR without treatment, moderate inflammation with dexpanthenol monotherapy and structural restoration in the mometasone furoate monotherapy and combination therapy groups. The best efficacy was observed in the combination therapy group, in which the histological pattern fully corresponded to the structure of the nasal mucosa of healthy animals, in contrast to mometasone furoate monotherapy, where histological signs of incomplete repair were observed. It should be noted that photoplethysmography also confirmed a statistically significant improvement in microcirculation in the combination therapy group compared with the control (p <0.05), approaching the indicators of healthy animals. The results of the study also proved the safety of the original intranasal combination. Conclusion. The drug combination has demonstrated superiority over monotherapy by the individual components included in its composition, providing hydration and restoration of the nasal mucosa, as well as normalization of microcirculation in it. The photoplethysmography method has shown its effectiveness for noninvasive assessment of blood flow in the nasal mucosa. The data obtained substantiate the prospects for further study of the above-mentioned combination therapy with intranasal administration to assess the efficacy and safety of MR treatment in clinical trials.

Keywords

• rhinitis medicamentosa
• nasal decongestants
• mometasone furoate
• dexpanthenol
• hyaluronic acid
• photoplethysmography