Experience with an optimized methodology of safety studies for pediatric medicines using the example of a drug containing cattle cerebral cortex polypeptides

A.V. Kalatanova1, ORCID: https://orcid.org/0000-0003-2623-6014

V.O. Nebogatikov2, ORCID: https://orcid.org/0000-0002-2454-9255

A.A. Nedorubov3,

A.R. Dorotenko1, ORCID: https://orcid.org/0000-0003-1142-6325

1Pharm-Holding, 198515, 34 A Svyazi Str., Strelna, Saint-Petersburg, Russia;

2Institute of Physiologically Active Substances of the Russian Academy of Sciences; 142432, Moscow region, Noginsky district, Chernogolovka, Severny proezd, 1;

3Sechenov First Moscow State Medical University 119991, 8-2 Trubetskaya str. Moscow, Russian Federation

Е-mail: Anna.Kalatanova@geropharm.com


This article presented the results of an experimental preclinical toxicological study of the drug containing cattle cerebral cortex polypeptides concerning the health indicators of immature animals. The study was carried out taking into account the recommendations of the current regulatory standards, as well as the 3R principles, to assess the safety with doses significantly higher than therapeutic doses in paediatry. The study was designed in such a way as to evaluate the possible toxic effect on the organism of juvenile animals of all pediatric age groups using standard toxicological methods, taking into account the age restrictions of the animals. For the study, an adapted scheme of injections was used: the test items was administered once to animals at the age of 30 days, repeatedly - starting from the 10th day after birth for 80 days, while the days corresponding to the completion of the next period of ontogenesis. According to the results of the study, it was the result, that the study item, with single and repeated administration in doses exceeding therapeutic doses, does not harm of immature rats. As a result, it was possible to comprehensively evaluate the possible toxic effect of the polypeptide preparation with a single administration to animals at the age of 30 days (children's age) and with repeated administration to animals at the age of 10-90 days (infancy-adolescence ages) with an emphasis on each age group separately. In this case, the most revealing study was the study with repeated administration, since it made it possible to simulate the continuous use of the drug throughout the entire period of growing up. Based on the results, it planning the experiment with the breeding of immature animals at the end of each subsequent period of ontogenesis seems to be the most humane design, which makes it possible to assess the toxic effect not only concerning different age groups of animals but also with different duration of administration: from 10 up to 80 days.

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Author Contributions 

A.V. Kalatanova, A.R. Dorotenko – writing the original text of the article;

V.O. Nebogatikov, A.A. Nedorubov – critical revision of the content of the article;

A.V. Kalatanova, V.O. Nebogatikov, A.A. Nedorubov – research planning, methodology, data processing, discussion of results, article editing$

V.O. Nebogatikov, A.A. Nedorubov, A.V. Kalatanova, A.R. Dorotenko – сollection, analysis or interpretation of study results.

Conflict of interest

The authors declare that there is no conflict of interest that requires disclosure in this article. The study was carried out with the financial support of  "Pharm-Holding". The authors of the article confirm the absence of a conflict of interest and their independence in preparing the content of the article, reviewing the article and forming conclusions.


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