Pharmacokinetics of K117 and K127, two novel antidote candidates to treat Tabun poisoning.

dc.contributor.author	Tekes, Kornélia
dc.contributor.author	Karvaly, Gellért
dc.contributor.author	Nurulain, Syed
dc.contributor.author	Kuca, Kamil
dc.contributor.author	Musilek, Kamil
dc.contributor.author	Adeghate, Ernest
dc.contributor.author	Jung, Young-Sik
dc.contributor.author	Kalász, Huba
dc.date.accessioned	2020-10-04T18:51:48Z
dc.date.available	2020-10-04T18:51:48Z
dc.date.issued	2019
dc.identifier	85069593247
dc.identifier.citation	journalVolume=310;pagination= Paper 108737, 5 pages;journalTitle=CHEMICO-BIOLOGICAL INTERACTIONS;journalAbbreviatedTitle=CHEM-BIOL INTERACT;
dc.identifier.uri	http://repo.lib.semmelweis.hu//handle/123456789/8132
dc.identifier.uri	doi:10.1016/j.cbi.2019.108737
dc.description.abstract	K117 and K127 are bis-pyridinium aldoximes but K117 is a bis-pyridinium bis-aldoxime while K127 has only one single aldoxime in addition to its amide substituent. Is there any difference in pharmacokinetics in these compounds that otherwise have the same chemical structure? Both K117 and K127 are developed as antidotes in acetylcholinesterase and butyrylcholinesterese poisoning in terrorist attacks or intoxication with other organophosphorous compounds. Their distributions have been scouted in the bodies of rats.White male Wistar rats were intramuscularly injected. The animals were sacrificed, tissue samples were homogenized, and either K117 or K127 concentrations were determined using reversed-phase high-performance liquid chromatography.Both K117 and K127 were present in all tissues that were analyzed including blood (serum), the brains, cerebrospinal fluid, the eyes, livers, kidneys, lungs and testes. Their pharmacokinetics and body distributions are similar.Either K117 or K127 meets the essential requirements for antidotes. Dose dependence and kinetics of their distribution were compared to that of other pyridinium aldoximes.
dc.title	Pharmacokinetics of K117 and K127, two novel antidote candidates to treat Tabun poisoning.
dc.type	Journal Article
dc.date.updated	2020-01-13T15:40:37Z
dc.language.rfc3066	en
dc.rights.holder	NULL
dc.identifier.mtmt	30733272
dc.identifier.wos	000482179600021
dc.identifier.pubmed	31279792
dc.contributor.department	SE/GYTK/Gyógyszerhatástani Intézet
dc.contributor.department	SE/AOK/I/Farmakológiai és Farmakoterápiás Intézet
dc.contributor.department	SE/AOK/I/Laboratóriumi Medicina Intézet
dc.contributor.institution	Semmelweis Egyetem
dc.mtmt.swordnote	Department of Pharmacodynamics, Semmelweis University, Nagyvárad tér 4, Budapest, H-1089, Hungary Department of Laboratory Medicine, Semmelweis University, Nagyvárad tér 4, Budapest, H-1089, Hungary Comsats, Islamabad, Pakistan Department of Chemistry, University of Hradec Kralove, Rokitanskeho 62, Hradec Kralove, 500 03, Czech Republic Department of Anatomy, United Arab Emirates University, Al Ain, United Arab Emirates Medicinal Science Division, Korea Research Institute of Chemical Technology, Daejeon, South Korea Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4, Budapest, H-1089, Hungary Export Date: 19 September 2019 CODEN: CBINA Correspondence Address: Kalász, H.; Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4, Hungary; email: drkalasz@gmail.com Funding Agency and Grant Number: Kalasz Teaching and Research Co. (Budapest, Hungary); Hungarian National Office for Research, Development and Innovation (Budapest, Hungary) [NN126968]; Ministry of Education, Youth and Sports of the Czech Republic [8F17004] Funding text: This project was part of a research cooperation among the Czech Republic, Hungary, the Korean Republic and Poland, and it was financially sponsored by Kalasz Teaching and Research Co. (Budapest, Hungary), by the NN126968 grant of the Hungarian National Office for Research, Development and Innovation (Budapest, Hungary) and by the Ministry of Education, Youth and Sports of the Czech Republic (no. 8F17004). Advice and help by Mr. Zoltan Szimrok, Mr. Janos Horvath, Mr. Andras Keglevich, Mrs. Gyorgyike Guth, Ms. Krisztina Kecskes and Mrs. Bogi Szalacsi are appreciated. Funding Agency and Grant Number: Kalasz Teaching and Research Co. (Budapest, Hungary); Hungarian National Office for Research, Development and Innovation (Budapest, Hungary) [NN126968]; Ministry of Education, Youth and Sports of the Czech RepublicMinistry of Education, Youth & Sports - Czech Republic [8F17004] Funding text: This project was part of a research cooperation among the Czech Republic, Hungary, the Korean Republic and Poland, and it was financially sponsored by Kalasz Teaching and Research Co. (Budapest, Hungary), by the NN126968 grant of the Hungarian National Office for Research, Development and Innovation (Budapest, Hungary) and by the Ministry of Education, Youth and Sports of the Czech Republic (no. 8F17004). Advice and help by Mr. Zoltan Szimrok, Mr. Janos Horvath, Mr. Andras Keglevich, Mrs. Gyorgyike Guth, Ms. Krisztina Kecskes and Mrs. Bogi Szalacsi are appreciated. Department of Pharmacodynamics, Semmelweis University, Nagyvárad tér 4, Budapest, H-1089, Hungary Department of Laboratory Medicine, Semmelweis University, Nagyvárad tér 4, Budapest, H-1089, Hungary Comsats, Islamabad, Pakistan Department of Chemistry, University of Hradec Kralove, Rokitanskeho 62, Hradec Kralove, 500 03, Czech Republic Department of Anatomy, United Arab Emirates University, Al Ain, United Arab Emirates Medicinal Science Division, Korea Research Institute of Chemical Technology, Daejeon, South Korea Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4, Budapest, H-1089, Hungary Export Date: 7 January 2020 CODEN: CBINA Correspondence Address: Kalász, H.; Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4, Hungary; email: drkalasz@gmail.com