Pharmacokinetics of Two Forms of Recombinant Insulin-Like Growth Factor 1 in the Mouse Blood

I. V. Dukhovlinov; O. A. Dobrovolskaya; I. V. Evsyukov; E. G. Bogomolova; N. N. Kolmakov; A. A. Lukovenko; E. A. Fedorova; S. A. Ishchuk; A. I. Orlov; E. V. Vorobeychikov; A. S. Simbirtsev

doi:10.1134/S1990519X19060038

Pharmacokinetics of Two Forms of Recombinant Insulin-Like Growth Factor 1 in the Mouse Blood

作者: Dukhovlinov I.V.¹, Dobrovolskaya O.A.², Evsyukov I.V.¹, Bogomolova E.G.², Kolmakov N.N.², Lukovenko A.A.³, Fedorova E.A.³, Ishchuk S.A.², Orlov A.I.⁴, Vorobeychikov E.V.⁵, Simbirtsev A.S.²
隶属关系:
1. LLC ATG Service Gene
2. Institute of Experimental Medicine
3. LLC Biochemical Agent
4. LLC Dakra Medical
5. LLC Polypharm
期: 卷 13, 编号 6 (2019)
页面: 457-462
栏目: Article
URL: https://ogarev-online.ru/1990-519X/article/view/213034
DOI: https://doi.org/10.1134/S1990519X19060038
ID: 213034

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The pharmacokinetics of two substances containing recombinant insulin-like growth factor 1 (IGF1) as an active substance was considered. The first substance (IGF₁) contains the actual recombinant IGF1, and the second (IGF₂) contains IGF1, which is translated from plasmid DNA encoding the IGF-1 gene for this protein. It was established that, with intramuscular administration of IGF₁, the delay time for its entry into the bloodstream is 1.5–2 h, while that with IGF₂ is 24–25 h. This indicates the presence of various mechanisms of accumulation of these substances in the systemic circulation. The maximum concentration of IGF₁ in the blood was determined 5 h after administration and that of IGF₂ was determined 125 h after administration. The maximum concentrations of these substances are comparable to each other. The concentration of IGF₁ in the blood decreases to its initial value 12 h after its administration, and the concentration of IGF₂ does so after 216 h. The clearance parameters (Cl) and elimination constants (Kel) of the considered substances also had significant differences, which confirms the presence of fast and slow dynamics of the decrease of their maximum concentrations after intramuscular injection. The different dynamics of the accumulation of substances in the blood and their elimination from the bloodstream after administration, as well as the different values of the area parameters under the pharmacokinetic curve (AUC_t, AUC_∞) demonstrate that IGF₂ has been in the systemic circulation for a longer time than IGF₁. This is essential for the appearance and severity of pharmacodynamic effects.

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pharmacokinetics, insulin-like growth factor, recombinant protein, plasmid DNA, IGF-1 gene, intramuscular injection

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Pharmacokinetics of Two Forms of Recombinant Insulin-Like Growth Factor 1 in the Mouse Blood

全文:

详细

关键词

作者简介

I. Dukhovlinov

O. Dobrovolskaya

I. Evsyukov

E. Bogomolova

N. Kolmakov

A. Lukovenko

E. Fedorova

S. Ishchuk

A. Orlov

E. Vorobeychikov

A. Simbirtsev

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