Antiviral inhalation medicinal product based on interferon alpha-2b: A study of efficacy, subchronic toxicity, and toxicokinetics in rodents

INTRODUCTION . Developing high-dose interferon-based medicinal products (MPs) is particularly relevant for effective causal treatment of acute respiratory viral infections, influenza, and COVID-19 coronavirus infection. Inhalation drops both act directly on mucous membranes and stimulate powerful immune response and increased safety profile. In 2021, a new medicinal product, interferon alpha-2b-based inhalation drops, was developed to treat influenza and acute respiratory viral infections of various aetiologies. AIM . This study aimed to assess preclinical efficacy, subchronic toxicity, and toxicokinetics of a new MP based on interferon alpha-2b and administered by inhalation. MATERIALS AND METHODS . The new MP is based on human recombinant interferon alpha-2b. Its efficacy was studied on female BALB/c mice. The animals inhaled 3 mL of the investigational product for 10 minutes twice a day for 8 days. Animals were infected with A(H1N1)pdm2009 on Day 2 of inhalation. The dynamics of body weight and mortality, as well as influenza titre in the murine lung tissues, were evaluated 4 days after infection. MP toxicity was studied on white non-linear rats of both sexes. MP was administered using an inhaler once a day for 7 weeks at doses exceeding human therapeutic dose by 5.3 and 53 times. Pathomorphological and histopathological examination was performed on Days 29 and 43 of administration. Haematological and biochemical blood parameters, heart rate, and behavioural functions were measured prior to administration, 4 weeks into administration, and 2 weeks after the last administration. Toxicokinetics was studied on satellite groups of male rats; administration scheme was similar to toxicity studies. RESULTS . Experiments showed that inhalation of investigational product at 923,000 IU/kg/day twice a day for 8 days inhibited A(H1N1)pdm2009 replication in the murine lungs, significantly reduced animal mortality and weight loss, and increased animal life expectancy 1.35–1.5-fold. The study doses showed no pronounced toxic, local irritant or systemic effect. CONCLUSIONS . The inhalation investigational product has shown its efficacy and safety in preclinical studies on rodents.