Pharmacokinetic profile of promising acetylcholinesterase reactivators K027 and K203 in experimental pigs
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F17%3A43875746" target="_blank" >RIV/60162694:G44__/17:43875746 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11150/17:10359332 RIV/00179906:_____/17:10359332
Result on the web
<a href="http://www.sciencedirect.com/science/article/pii/S0378427417301194#" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0378427417301194#</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.toxlet.2017.03.017" target="_blank" >10.1016/j.toxlet.2017.03.017</a>
Alternative languages
Result language
angličtina
Original language name
Pharmacokinetic profile of promising acetylcholinesterase reactivators K027 and K203 in experimental pigs
Original language description
Standard treatment of organophosphorus compounds (OPs) poisoning includes administration of an anti-muscarinic (atropine), anticonvulsive (diazepam) and acetylcholinesterase reactivator (oxime). From a wide group of newly synthesized oximes, oxime K027 and oxime K203 seem to be perspective compounds in some specific OPs intoxication. The available in vitro and in vivo preclinical data indicate that both oximes may be considered for potential human use. The main aim of this study was to establish plasmatic concentration curves of both oximes after intramuscular (i.m.) and intragastric(i.g.) application with subsequent pharmacokinetic analysis and study distribution after (i.m.) application on a non-rodent animal model (experimental pigs; 1500 mg/animal). According to the results, both oximes had similar C-max (K027: 106 +/- 19 mu g/mL and K203: 111 +/- 8 mu g/mL) in T-max 19 +/- 5 min, respectively, in 22 +/- 3 min. Bioavailability of oxime K027 calculated as AUC(total) (8389 +/- 1024 min mu g/mL) was halved compared to oxime K203 (16938 +/- 795 min mu g/mL). The highest concentration from peripheral tissues was found in the kidney and lung, but the brain concentrations stay very low, the plasma/brain ratio being approximately 1%. The applied doses were derived from the recommendation where it is possible to use three autoinjectors to save human life. The results provide us with knowledge about the pharmacokinetics and distribution of these new oximes and may help us to better estimate the human pharmacokinetic profile.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30108 - Toxicology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Toxicology Letters
ISSN
0378-4274
e-ISSN
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Volume of the periodical
273
Issue of the periodical within the volume
May
Country of publishing house
IE - IRELAND
Number of pages
6
Pages from-to
20-25
UT code for WoS article
000400459600003
EID of the result in the Scopus database
2-s2.0-85016417942