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Comparative Study
. 2024 Dec;519(1):525-533.
doi: 10.1134/S1607672924701151. Epub 2024 Oct 31.

A Study of the Comparability of the Pharmacodynamic, Toxicological, and Pharmacokinetic Properties of the Reference Drug Pulmozyme® and the Biosimilar Drug Tigerase®

M S Aksenova  1 , E N Bocharova  1 , S G Abbasova  2 , A S Ponomarev  3 , V V Loginova  1 , M V Bolotnikova  1 , N V Belskaya  1 , A A Kazarov  1 , A E Lisova  1 , N K Kudina  1 , M S Pantyushenko  1 , M V Zhilyaeva  1 , D S Kopein  1 , Yu M Karelov  3 , G G Erastov  3 , M V Lykov  1 , R A Khamitov  1
Affiliations
Comparative Study

A Study of the Comparability of the Pharmacodynamic, Toxicological, and Pharmacokinetic Properties of the Reference Drug Pulmozyme® and the Biosimilar Drug Tigerase®

M S Aksenova et al. Dokl Biochem Biophys. 2024 Dec.

Abstract

The article presents the results of studies of the drug Tigerase® (inhalation solution manufactured by JSC GENERIUM, Russia), conducted to obtain evidence of its similarity (comparability) to the reference drug Pulmozyme® (inhalation solution, manufactured by Hoffmann-La Roche Ltd., Switzerland). Both drugs contain human recombinant deoxyribonuclease I (dornase alfa) as an active substance and are intended for the treatment of cystic fibrosis with pulmonary manifestations (mucoviscidosis). The enzymatic activity of dornase alfa, contained in the studied drugs, was investigated in vitro and ex vivo on samples of purulent sputum of patients. The pharmacokinetic parameters of the drugs in the blood serum, bronchi, and lungs, as well as the main physiological parameters (body weight and temperature, the state of the cardiovascular, respiratory, excretory systems, hematological and biochemical blood parameters, pathomorphological changes in internal organs (including the state of the cornea), and mortality rates) were investigated in comparative studies of subchronic toxicity in juvenile and mature rats with 28-day inhalation at doses of 0.2 mg/kg for mature animals and 0.26 mg/kg for juvenile animals (the dose was 6 times higher than the dose recommended for clinical use). The results of the studies allow us to conclude that the drugs are comparable in enzymatic, mucolytic (secretolytic) DNase activity, safety profile and main pharmacokinetic parameters.

Keywords: DNase activity; biosimilar; cystic fibrosis; dornase alfa.

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Conflict of interest statement

ETHICS APPROVAL AND CONSENT TO PARTICIPATE: When conducting experiments with animals, all provisions of the “Policy for Working with Laboratory Animals of the Testing Center of the Preclinical Research Center of JSC GENERIUM, based on the main international standards "Directive 2010/63/EU of the European Parliament” and of the Council of 22.09.2010 “On the Protection of Animals used for Scientific Purposes”, and Appendix A to the “European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes” (ETS No. 123), were observed. Guidelines for the Care and Maintenance of Laboratory Animals (Article no. 5 of the Convention). The main conditions for keeping and handling animals, taking into account the “Three R” concept, were set out in the veterinary protocol, which was reviewed and approved by the Bioethics Commission of JSC GENERIUM (Minutes of the meeting of the Bioethics Commission No. 28/2014 dated October 17, 2014). No deviations from the veterinary protocol were found during the experiments. The authors confirm that the established ethical norms and standards for working with animals were observed during the experiments using animals. CONFLICT OF INTEREST: The authors of this work declare that they have no conflicts of interest.

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