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 (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.

中文翻译：

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两种形式的重组胰岛素样生长因子1在小鼠血液中的药代动力学

摘要

考虑了以重组胰岛素样生长因子1（IGF1）为有效成分的两种物质的药代动力学。第一种物质（IGF ₁）包含实际的重组IGF1，第二种物质（IGF ₂）包含IGF1，它是从编码该蛋白质的IGF-1基因的质粒DNA中翻译而来的。已经确定，肌肉注射IGF ₁时，其进入血流的延迟时间为1.5–2 h，而IGF _2时为24–25 h。这表明在体循环中存在这些物质积累的各种机制。IGF ₁的最大浓度在给药后5小时测定血液中的血脂，在给药后125小时测定IGF ₂的血。这些物质的最大浓度彼此相当。给药后12小时，血液中IGF ₁的浓度降低至其初始值，而216小时后，IGF ₂的浓度下降。间隙参数（Cl）和消除常数（Kel）中所考虑的物质也具有显着差异，这证实了在肌肉内注射后其最大浓度下降的快慢动力学变化。的物质在血液中积累，并从给药后血液中消除它们的不同动力学，以及药代动力学曲线下面积参数的不同的值（AUC_吨，AUC _∞）表明，IGF ₂已经在全身循环的时间比IGF _1长。这对于药效学作用的出现和严重程度至关重要。