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Translation of in vitro to in vivo pyridinium oxime potential in tabun poisoning (CROSBI ID 223851)

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Katalinić, Maja ; Maček Hrvat, Nikolina ; Ždarova Karasova, Jana ; Misik, Jan ; Kovarik, Zrinka Translation of in vitro to in vivo pyridinium oxime potential in tabun poisoning // Arhiv za higijenu rada i toksikologiju, 66 (2015), 285-292. doi: 10.1515/aiht-2015-66-2740

Podaci o odgovornosti

Katalinić, Maja ; Maček Hrvat, Nikolina ; Ždarova Karasova, Jana ; Misik, Jan ; Kovarik, Zrinka

engleski

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

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.

acetylcholinesterase ; antidotes ; butyrylcholinesterase ; K048 ; nerve agents ; pharmacokinetics ; tissue-specific activity

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Podaci o izdanju

66

2015.

285-292

objavljeno

0004-1254

1848-6312

10.1515/aiht-2015-66-2740

Povezanost rada

Kemija, Biologija, Temeljne medicinske znanosti

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