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

• Published in: Cell and tissue biology Vol. 13; no. 6; pp. 457 - 462
• Main Authors: Dukhovlinov, I. V., Dobrovolskaya, O. A., Evsyukov, I. V., Bogomolova, E. G., Kolmakov, N. N., Lukovenko, A. A., Fedorova, E. A., Ishchuk, S. A., Orlov, A. I., Vorobeychikov, E. V., Simbirtsev, A. S.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 2019; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Blood; Cell Biology; Insulin; Insulin-like growth factor I; Insulin-like growth factor II; Insulin-like growth factors; Life Sciences; Pharmacodynamics; Pharmacokinetics; pharmacokinetics; plasmid DNA; insulin-like growth factor; intramuscular injection; gene; recombinant protein
• ISSN: 1990-519X; 1990-5203
• DOI: 10.1134/S1990519X19060038

The pharmacokinetics of two substances containing recombinant insulin-like growth factor 1 (IGF1) as an active substance was considered. The first substance (IGF 1 ) contains the actual recombinant IGF1, and the second (IGF 2 ) contains IGF1, which is translated from plasmid DNA encoding the IGF-1 gene for this protein. It was established that, with intramuscular administration of IGF 1 , the delay time for its entry into the bloodstream is 1.5–2 h, while that with IGF 2 is 24–25 h. This indicates the presence of various mechanisms of accumulation of these substances in the systemic circulation. The maximum concentration of IGF 1 in the blood was determined 5 h after administration and that of IGF 2 was determined 125 h after administration. The maximum concentrations of these substances are comparable to each other. The concentration of IGF 1 in the blood decreases to its initial value 12 h after its administration, and the concentration of IGF 2 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 IGF 2 has been in the systemic circulation for a longer time than IGF 1 . This is essential for the appearance and severity of pharmacodynamic effects.