Investigation of the pharmacokinetic parameters of poloxamer-modified hyaluronidase during different routes of administration
Author Affiliations1Novosibirsk State Medical University of Minzdrav of Russia, 630091, Novosibirsk, Krasny av., 52
2Novosibirsk State Medical University of Minzdrav of Russia, 630091, Novosibirsk, Krasny av., 52
3Novosibirsk State Medical University of Minzdrav of Russia, 630091, Novosibirsk, Krasny av., 52
4Novosibirsk State Medical University of Minzdrav of Russia, 630091, Novosibirsk, Krasny av., 52
5Novosibirsk State Medical University of Minzdrav of Russia, 630091, Novosibirsk, Krasny av., 52
Abstract
In experimental work on rats main pharmacokinetic parameters of poloxamer-modified hyaluronidase (PMH) were investigated during intragastric and intravenouse routes of administration. Intravenous injection has been found to be ineffective, since PMH weakly penetrates into tissues and is rapidly excreted. PMH enteral administration is followed by the absolute bioavailability of 23.97 %, the circulation time in blood plasma of 6 hours, the maximum concentration of 55.99 μg/ml, which is reached after 2 hours; the highest PMH level was found in the liver and kidneys. It is concluded that, from the point of view of clinical PGM positioning, the enteral route of delivery is optimal.
Key words
References
- Dygai A.M., Skurikhin E.G., Ermakova N.N. et al. Antifibrotic effects of immobilized hyaluronidase in repeated bleomycin-induced lesions of the alveolar epithelium // Byul.eksperim.biol. i med. = Bull. Exp. Biol. Med. 2013. 155. (4). 501–506. [In Russian]
- Dygai A.M., Skurikhin E.G., Khmelevskaya E.S. et al. Effect of immobilized hyaluronidase on stem and progenitor cells in pulmonary fibrosis // Kletoch.tekhnol. v biol. i med. = Cellular Technol. in Biol. and Med. 2013. (4). 244–249. [In Russian]
- Dygai A.M., Zyuz'kov G.N., Gurto R.V. et al. Effect of hyaluronate-endo-β-N-acetylhexosaminidase pegylated by electron beam synthesis nanotechnology on the formation of hematological shifts in chronic hepatitis // Byul.eksperim.biol. i med =Bul. Exp. Biol. Med. 2013. 154. (2). 278–282. [In Russian]
- Dygai A.M., Zyuz'kov G.N., Gurto R.V. et al. Effect of pegylated hyaluronate-endo-β-N-acetylhexosaminidase on humoral mechanisms regulating the functions of progenitor cells during chronic hepatitis // Byul.eksperim.biol. i med. = Bul. Exp. Biol. Med. 2013. 155. (2). 179–182. [In Russian]
- Dygai A.M., Zyuz'kov G.N., Zhdanov V.V. et al. Effect of hyaluronidase immobilized using electron-beam synthesis nanotechnology on sensitivity of progenitor cells to regulatory factors // Byul.eksperim.biol. i med. = Bull. Exp. Biol. Med. 2011. 151. (1). 150–153. [In Russian]
- Jin W.P., Sang K.K., Taslim A.A. et al. Strategies for oral delivery of macromolecule drugs // Biotechnol. Bioprocess Eng. 2010. 15. (4). 66–75.
- Kabanov A.V., Batrakova E.V., Alakhov V.Y. Pluronic® block copolymers as novel polymer therapeutics for drug and gene delivery // J. Control. Release. 2002. 82. (2–3). 189–212.
- Madonov P.G., Ershov K.I., Dubrovin A.V. et al. Electron-beam modification of preparations of the albuminous nature for improvement of their pharmacological properties. // Meditsina i obrazovanie v Sibiri = Medicine and Education in Siberia. 2013. (4). http://www.ngmu.ru/cozo/mos/article/pdf.php?id=1115. [In Russian].
- Sharma R.K., Sharma M. Polyethylene oxide-polypropylene oxide based block copolymers as nanovehicles for drug formulations // BioEvolution. 2014. 1. (3). 68–75.
- Shilova M.A., Grek O.R., Madonov P.G. Studying the parameters of enteral transport of modified hyaluronidasum forms // Meditsina i obrazovanie v Sibiri = Medicine and Education in Siberia. 2015. (3). http://www.ngmu.ru/cozo/mos/article/text_full.php?id=1751. [In Russian].
- Skurihin E.G., Pershina O.V., Krupin V.A. et al. Effects and mechanisms of pegylated hyaluronidaze in C57BL/6 mice under bleomycin induced pulmonary fibrosis // Patogenez = Pathogenesis. 2015. (3). 56–64. [In Russian].
- Skurikhin E.G., Reztsova A.M., Ermakova N.N. et al. Antifibrotic activity of conjugates based on amphiphilic pluronic F68 and hydrophobic pluronic L31 with hyaluronate-endo-β-N-acetylhexosaminidase in pulmonary fibrosis // Byul.eksperim.biol. i med =Bull. Exp. Biol. Med. 2014. 157. (1). 5–9. [In Russian]
About Authors (Correspondence):
Shilova M.A. – postgraduate student of the chair for pharmacology, clinical pharmacology and evidentiary medicine, e-mail: pharmacevt85@list.ru
Yershov K.I. – candidate of medical sciences, assistant of the chair for pharmacology, clinical pharmacology and evidentiary medicine
Grek O.R. – doctor of medical sciences, professor of the chair for pharmacology, clinical pharmacology and evidentiary medicine
Madonov P.G. – doctor of medical sciences, professor, head of the chair for pharmacology, clinical pharmacology and evidentiary medicine
Fil’ M.E. – 4th year student of the medical faculty