A study of the nuclease activity in the plasma of children and adolescents with cystic fibrosis (CF) during therapy with Dornase alpha was carried out. The level of nuclease activity was measured in 35 patients after inhalation of Dornase alpha. An increase in the level of nuclease activity of blood plasma after inhalation of Dornase alpha by patients with cystic fibrosis was obtained. High variability was observed in the dynamics of changes in the level of nuclease activity during therapy with the inhaled drug Dornase alpha. According to the period of reaching the peak level of nuclease activity after inhalation of the drug (Tmax), the patients were divided into 4 groups: Tmax 1.5 hours (1 group), Tmax 3.0 hours (2 group), Tmax 4,5 hours (3 group), Tmax 6.0 hours (4 group). The change of the area under the curve (AUC) «nuclease activity - time» (ng•h/ml) in 88.59 % of cases and the PK parameter - peak nuclease activity (Cmax, ng/ml) in 89.17 % is determined by the BMI parameter (p<0.0001). Higher AUC values of nuclease activity - time (ng•h/ml) in girls were obtained. Significantly lower values of AUC «nuclease activity - time» (ng•h/ml) and Cmax, ng/ml were found in patients who received inhaled glucocorticosteroids (IGCS) in therapy (p<0.05). The level of nuclease activity during inhalation of Dornase alfa in patients with CF depends on gender, BMI and IGCS therapy, which should be taken into account when prescribing this drug. The inhalation time can be selected according to the possibilities of the patient's daily routine. © 2020 Stavropol State Medical University. All rights reserved.