Pharmacokinetics of Recombinant Human Tumor Necrosis Factor Alpha in the Delivery System
| Autor: | A. V. Bateneva, O. V. Simakova, S. G. Gamaley, E. A. Volosnikova, L. R. Lebedev, E. D. Danilenko |
|---|---|
| Jazyk: | ruština |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Drug Proteases outbred mice media_common.quotation_subject Spleen Absorption (skin) Pharmacology delivery system law.invention 03 medical and health sciences 0302 clinical medicine Pharmacokinetics law medicine media_common tumor necrosis factor alpha Chemistry molecular construct 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Automotive Engineering Recombinant DNA Medicine Tumor necrosis factor alpha Delivery system pharmacokinetics TP248.13-248.65 Biotechnology |
| Zdroj: | Биопрепараты: Профилактика, диагностика, лечение, Vol 19, Iss 3, Pp 169-177 (2019) |
| ISSN: | 2619-1156 |
| Popis: | The main problems of using TNF-alpha in antitumor therapy are its rapid degradation in the bloodstream and the limited selectivity of accumulation in the tumor tissue. The SRC VB «Vector» developed a biodegradable molecular construct that provides protection against proteases and ensures targeted delivery of proteins to the tumor tissue. This construct was used to create an antitumor drug containing recombinant human TNF-alpha (rhTNF-alpha).The aim of the study was to analyse rhTNF-alpha pharmacokinetics in the delivery system after a single administration.Materials and methods: the rhTNF-alpha drug carried by the delivery system was intravenously administered to female outbred ICR (СD-1) mice only once at two effective antitumor doses, 2.55 μg and 5.1 μg / 20 g of body weight. The concentration of TNF-alpha in the serum and supernatants of organ homogenates, obtained at different time points after administration, was analysed by immunoenzyme assay.Results: the obtained curves of TNF-alpha concentration in the blood were satisfactorily described by the equation for the twocompartment model without absorption. The rapid phase of elimination from the blood took 0–4 h, the slow one — 4–24 h. The highest specific content of protein was observed in the skin, spleen, and kidneys tissue. The calculation of pharmacokinetic parameters demonstrated that the highest values of tissue availability fT were obtained for the kidneys and skin; the drug was retained for longer periods of time in the kidneys, liver and skin (according to the MRT data). As a rule, complete elimination of the drug was observed by the end of the first day after administration.Conclusions: rhTNF-alpha carried by the delivery system was quickly eliminated from the blood and distributed in the internal organ tissues after a single intravenous administration to mice in the effective doses range. The main organs in which rhTNF-alpha was distributed were skin, kidneys, and spleen. The elimination of the drug from the blood was a two-phase process which was generally over by the end of the first day. |
| Databáze: | OpenAIRE |
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