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https://doi.org/10.1515/aiht-2015-66-2740

Translation of in vitro to in vivo pyridinium oxime potential in tabun poisoning

Maja Katalinić   ORCID icon orcid.org/0000-0001-7043-4291 ; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Nikolina Maček Hrvat   ORCID icon orcid.org/0000-0003-1682-8999 ; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Jana Žďárová Karasová ; Faculty of Military Health Sciences, Hradec Kralove, Czech Republic
Jan Misik ; Faculty of Military Health Sciences, Hradec Kralove, Czech Republic
Zrinka Kovarik   ORCID icon orcid.org/0000-0001-9863-886X ; Institute for Medical Research and Occupational Health, Zagreb, Croatia

Puni tekst: engleski, pdf (573 KB) str. 291-298 preuzimanja: 167* citiraj
APA 6th Edition
Katalinić, M., Maček Hrvat, N., Žďárová Karasová, J., Misik, J. i Kovarik, Z. (2015). Translation of in vitro to in vivo pyridinium oxime potential in tabun poisoning. Arhiv za higijenu rada i toksikologiju, 66 (4), 291-298. https://doi.org/10.1515/aiht-2015-66-2740
MLA 8th Edition
Katalinić, Maja, et al. "Translation of in vitro to in vivo pyridinium oxime potential in tabun poisoning." Arhiv za higijenu rada i toksikologiju, vol. 66, br. 4, 2015, str. 291-298. https://doi.org/10.1515/aiht-2015-66-2740. Citirano 21.11.2019.
Chicago 17th Edition
Katalinić, Maja, Nikolina Maček Hrvat, Jana Žďárová Karasová, Jan Misik i Zrinka Kovarik. "Translation of in vitro to in vivo pyridinium oxime potential in tabun poisoning." Arhiv za higijenu rada i toksikologiju 66, br. 4 (2015): 291-298. https://doi.org/10.1515/aiht-2015-66-2740
Harvard
Katalinić, M., et al. (2015). 'Translation of in vitro to in vivo pyridinium oxime potential in tabun poisoning', Arhiv za higijenu rada i toksikologiju, 66(4), str. 291-298. https://doi.org/10.1515/aiht-2015-66-2740
Vancouver
Katalinić M, Maček Hrvat N, Žďárová Karasová J, Misik J, Kovarik Z. Translation of in vitro to in vivo pyridinium oxime potential in tabun poisoning. Arh Hig Rada Toksikol. [Internet]. 2015 [pristupljeno 21.11.2019.];66(4):291-298. https://doi.org/10.1515/aiht-2015-66-2740
IEEE
M. Katalinić, N. Maček Hrvat, J. Žďárová Karasová, J. Misik i Z. Kovarik, "Translation of in vitro to in vivo pyridinium oxime potential in tabun poisoning", Arhiv za higijenu rada i toksikologiju, vol.66, br. 4, str. 291-298, 2015. [Online]. https://doi.org/10.1515/aiht-2015-66-2740

Sažetak
Even if organophosphorus (OP) nerve agents were banned entirely, their presence would remain a problem as weapons of terror (like in Syria). Oxime antidotes currently used in medical practice still fall short of their therapeutic purpose, as they fail to fully restore the activity of cholinesterases, the main target for OPs. As orphan drugs, these antidotes are tested too seldom for anybody’s benefit. Over the last few decades, search for improved reactivators has reached new levels, but the translation of data obtained in vitro to in vivo application is still a problem that hinders efficient therapy. In this study, we tested the strengths and weaknesses of extrapolating pyridinium oxime antidotes reactivation efficiency from in vitro to in vivo application. Our results show that this extrapolation is possible with well-determined kinetic constants, but that it also largely depends on oxime circulation time and its tissue-specific distribution. This suggests that pharmacokinetic studies should be planned at the early stages of antidote development. Special attention should also be given to improving oxime distribution throughout the organism to overcome this major constraint in improving overall OP therapy.

Ključne riječi
acetylcholinesterase; antidotes; butyrylcholinesterase; K048; nerve agents; pharmacokinetics, tissuespecific activity

Hrčak ID: 149581

URI
https://hrcak.srce.hr/149581

[hrvatski]

Posjeta: 355 *