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


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Abstract

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 (AUCt, 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.

About the authors

I. V. Dukhovlinov

LLC ATG Service Gene

Email: evsyukov007@mail.ru
Russian Federation, St. Petersburg, 199034

O. A. Dobrovolskaya

Institute of Experimental Medicine

Email: evsyukov007@mail.ru
Russian Federation, St. Petersburg, 197376

I. V. Evsyukov

LLC ATG Service Gene

Author for correspondence.
Email: evsyukov007@mail.ru
Russian Federation, St. Petersburg, 199034

E. G. Bogomolova

Institute of Experimental Medicine

Email: evsyukov007@mail.ru
Russian Federation, St. Petersburg, 197376

N. N. Kolmakov

Institute of Experimental Medicine

Email: evsyukov007@mail.ru
Russian Federation, St. Petersburg, 197376

A. A. Lukovenko

LLC Biochemical Agent

Email: evsyukov007@mail.ru
Russian Federation, St. Petersburg, 190005

E. A. Fedorova

LLC Biochemical Agent

Email: evsyukov007@mail.ru
Russian Federation, St. Petersburg, 190005

S. A. Ishchuk

Institute of Experimental Medicine

Email: evsyukov007@mail.ru
Russian Federation, St. Petersburg, 197376

A. I. Orlov

LLC Dakra Medical

Email: evsyukov007@mail.ru
Russian Federation, St. Petersburg, 197101

E. V. Vorobeychikov

LLC Polypharm

Email: evsyukov007@mail.ru
Russian Federation, St. Petersburg, 197101

A. S. Simbirtsev

Institute of Experimental Medicine

Email: evsyukov007@mail.ru
Russian Federation, St. Petersburg, 197376

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