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

IF 0.8 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Doklady Biochemistry and Biophysics Pub Date : 2024-10-31 DOI:10.1134/S1607672924701151

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

{"title":"A Study of the Comparability of the Pharmacodynamic, Toxicological, and Pharmacokinetic Properties of the Reference Drug Pulmozyme® and the Biosimilar Drug Tigerase®.","authors":"M S Aksenova, E N Bocharova, S G Abbasova, A S Ponomarev, V V Loginova, M V Bolotnikova, N V Belskaya, A A Kazarov, A E Lisova, N K Kudina, M S Pantyushenko, M V Zhilyaeva, D S Kopein, Yu M Karelov, G G Erastov, M V Lykov, R A Khamitov","doi":"10.1134/S1607672924701151","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8000,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Doklady Biochemistry and Biophysics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1134/S1607672924701151","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

参考药物 Pulmozyme® 和生物类似药 Tigerase® 的药效学、毒理学和药代动力学特性的可比性研究。

文章介绍了对药物Tigerase®（由俄罗斯JSC GENERIUM公司生产的吸入溶液）的研究结果，该研究旨在获得其与参考药物Pulmozyme®（由瑞士Hoffmann-La Roche有限公司生产的吸入溶液）相似性（可比性）的证据。这两种药物都含有作为活性物质的人重组脱氧核糖核酸酶 I（多酶α），用于治疗有肺部表现的囊性纤维化（粘液粘稠病）。对所研究药物中含有的多纳酶 alfa 的酶活性进行了体外和体内研究，研究对象是患者的脓痰样本。在对幼年大鼠和成年大鼠进行的亚慢性毒性比较研究中，对血清、支气管和肺中的药物药代动力学参数以及主要生理参数（体重和体温，心血管、呼吸、排泄系统的状态，血液学和生化血液参数，内脏器官的病理形态学变化（包括角膜状态）和死亡率）进行了调查。成年大鼠的吸入剂量为 0.2 毫克/千克，幼年大鼠的吸入剂量为 0.26 毫克/千克（该剂量是临床建议使用剂量的 6 倍）。研究结果使我们得出结论，这两种药物在酶活性、粘液溶解（分泌溶解）DNase 活性、安全性和主要药代动力学参数方面具有可比性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Doklady Biochemistry and Biophysics 生物-生化与分子生物学

CiteScore

1.60

自引率

12.50%

发文量

审稿时长

6-12 weeks

期刊介绍： Doklady Biochemistry and Biophysics is a journal consisting of English translations of articles published in Russian in biochemistry and biophysics sections of the Russian-language journal Doklady Akademii Nauk. The journal''s goal is to publish the most significant new research in biochemistry and biophysics carried out in Russia today or in collaboration with Russian authors. The journal accepts only articles in the Russian language that are submitted or recommended by acting Russian or foreign members of the Russian Academy of Sciences. The journal does not accept direct submissions in English.