SAFETY STUDY OF ROMIPLOSTIM BIOSIMILAR

Idiopathic thrombocytopenic purpura is a chronic autoimmune hematological disease caused by an increased destruction of platelets and associated thrombocytopenia, for the treatment of which the imported drug romiplostim is used. Сreation of the drug biosimilar provides a reduction in the cost of the...

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Main Authors: A. N. Afanasyeva, V. B. Saparova, D. D. Karal-Ogly, E. I. Mukhametzyanova, D. V. Kurkin, A. V. Kalatanova, I. E. Makarenko, A. L. Khokhlov, I. A. Lugovik
Format: Article
Language:Russian
Published: Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute 2022-10-01
Series:Фармация и фармакология (Пятигорск)
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Online Access:https://www.pharmpharm.ru/jour/article/view/1165
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author A. N. Afanasyeva
V. B. Saparova
D. D. Karal-Ogly
E. I. Mukhametzyanova
D. V. Kurkin
A. V. Kalatanova
I. E. Makarenko
A. L. Khokhlov
I. A. Lugovik
author_facet A. N. Afanasyeva
V. B. Saparova
D. D. Karal-Ogly
E. I. Mukhametzyanova
D. V. Kurkin
A. V. Kalatanova
I. E. Makarenko
A. L. Khokhlov
I. A. Lugovik
author_sort A. N. Afanasyeva
collection DOAJ
description Idiopathic thrombocytopenic purpura is a chronic autoimmune hematological disease caused by an increased destruction of platelets and associated thrombocytopenia, for the treatment of which the imported drug romiplostim is used. Сreation of the drug biosimilar provides a reduction in the cost of therapy and an access for the treatment to more patients.The aim of the study was to compare the safety indicators of the reference drug and its biosimilar in vivo and in vitro.Materials and methods. In the in vitro study, a model of “complement-dependent cytotoxicity” induced by the complement was formed on the 32D hTPOR clone 63-cell line, followed by a cell viability measurement with the CellTitter Glo® kit. An in vivo part of the study was carried out on Javanese macaque monkeys (Macaca fascicularis). During the experiment, the clinical condition, mortality, appetite of the animals, their body weight, body temperature, respiratory rate were assessed, the clinical parameters of blood and urine of the animals were also monitored, and the hemostasis indicators were additionally measured.Results. In the in vitro experiment, the original drug romiplostim and its biosimilar GP40141 were compared in terms of EC50 values. The indicatirs did not show complement-dependent cytotoxicity. According to the in vivo results, no deviations were recorded in the clinical status of the animals and their feed intake, and no lethality was fixed out in the groups either. For all the parameters studied (body weight and temperature, respiratory rate, clinical urinalysis, clinical and biochemical blood tests, coagulation hemostasis), GP40141 and romiplostim, when administered at the doses equivalent to 10 toxic doses (TDs), had comparable effects.Conclusion. In the comparison of safety performance both in vitro and in vivo, the original drug romiplostim and its biosimilar GP40141 showed similar results.
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spelling doaj-art-a5cc49ccab96497c88981a4904fcda8c2025-08-20T03:59:56ZrusVolgograd State Medical University, Pyatigorsk Medical and Pharmaceutical InstituteФармация и фармакология (Пятигорск)2307-92662413-22412022-10-0110435437010.19163/2307-9266-2022-10-4-354-370449SAFETY STUDY OF ROMIPLOSTIM BIOSIMILARA. N. Afanasyeva0V. B. Saparova1D. D. Karal-Ogly2E. I. Mukhametzyanova3D. V. Kurkin4A. V. Kalatanova5I. E. Makarenko6A. L. Khokhlov7I. A. Lugovik8Сlosed Joint-Stock Company “Farm-Holding”Сlosed Joint-Stock Company “Farm-Holding”; A.I. Yevdokimov Moscow State University of Medicine and DentistryScientific Research Institute of Medical PrimatologyScientific Research Institute of Medical PrimatologyVolgograd State Medical UniversityСlosed Joint-Stock Company “Farm-Holding”Сlosed Joint-Stock Company “Farm-Holding”; A.I. Yevdokimov Moscow State University of Medicine and DentistryYaroslavl State Medical UniversityСlosed Joint-Stock Company “Farm-Holding”Idiopathic thrombocytopenic purpura is a chronic autoimmune hematological disease caused by an increased destruction of platelets and associated thrombocytopenia, for the treatment of which the imported drug romiplostim is used. Сreation of the drug biosimilar provides a reduction in the cost of therapy and an access for the treatment to more patients.The aim of the study was to compare the safety indicators of the reference drug and its biosimilar in vivo and in vitro.Materials and methods. In the in vitro study, a model of “complement-dependent cytotoxicity” induced by the complement was formed on the 32D hTPOR clone 63-cell line, followed by a cell viability measurement with the CellTitter Glo® kit. An in vivo part of the study was carried out on Javanese macaque monkeys (Macaca fascicularis). During the experiment, the clinical condition, mortality, appetite of the animals, their body weight, body temperature, respiratory rate were assessed, the clinical parameters of blood and urine of the animals were also monitored, and the hemostasis indicators were additionally measured.Results. In the in vitro experiment, the original drug romiplostim and its biosimilar GP40141 were compared in terms of EC50 values. The indicatirs did not show complement-dependent cytotoxicity. According to the in vivo results, no deviations were recorded in the clinical status of the animals and their feed intake, and no lethality was fixed out in the groups either. For all the parameters studied (body weight and temperature, respiratory rate, clinical urinalysis, clinical and biochemical blood tests, coagulation hemostasis), GP40141 and romiplostim, when administered at the doses equivalent to 10 toxic doses (TDs), had comparable effects.Conclusion. In the comparison of safety performance both in vitro and in vivo, the original drug romiplostim and its biosimilar GP40141 showed similar results.https://www.pharmpharm.ru/jour/article/view/1165romiplostimbiosimilar gp40141nplate®complement-dependent cytotoxicitydrug safety studiesin vivoin vitroidiopathic thrombocytopenic purpuratoxicological profilethrombopoietin receptortpo-r
spellingShingle A. N. Afanasyeva
V. B. Saparova
D. D. Karal-Ogly
E. I. Mukhametzyanova
D. V. Kurkin
A. V. Kalatanova
I. E. Makarenko
A. L. Khokhlov
I. A. Lugovik
SAFETY STUDY OF ROMIPLOSTIM BIOSIMILAR
Фармация и фармакология (Пятигорск)
romiplostim
biosimilar gp40141
nplate®
complement-dependent cytotoxicity
drug safety studies
in vivo
in vitro
idiopathic thrombocytopenic purpura
toxicological profile
thrombopoietin receptor
tpo-r
title SAFETY STUDY OF ROMIPLOSTIM BIOSIMILAR
title_full SAFETY STUDY OF ROMIPLOSTIM BIOSIMILAR
title_fullStr SAFETY STUDY OF ROMIPLOSTIM BIOSIMILAR
title_full_unstemmed SAFETY STUDY OF ROMIPLOSTIM BIOSIMILAR
title_short SAFETY STUDY OF ROMIPLOSTIM BIOSIMILAR
title_sort safety study of romiplostim biosimilar
topic romiplostim
biosimilar gp40141
nplate®
complement-dependent cytotoxicity
drug safety studies
in vivo
in vitro
idiopathic thrombocytopenic purpura
toxicological profile
thrombopoietin receptor
tpo-r
url https://www.pharmpharm.ru/jour/article/view/1165
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AT vbsaparova safetystudyofromiplostimbiosimilar
AT ddkaralogly safetystudyofromiplostimbiosimilar
AT eimukhametzyanova safetystudyofromiplostimbiosimilar
AT dvkurkin safetystudyofromiplostimbiosimilar
AT avkalatanova safetystudyofromiplostimbiosimilar
AT iemakarenko safetystudyofromiplostimbiosimilar
AT alkhokhlov safetystudyofromiplostimbiosimilar
AT ialugovik safetystudyofromiplostimbiosimilar