-
Something wrong with this record ?
Pharmacokinetic profile of promising acetylcholinesterase reactivators K027 and K203 in experimental pigs
JZ. Karasova, J. Kvetina, I. Tacheci, V. Radochova, K. Musilek, K. Kuca, J. Bures,
Language English Country Netherlands
Document type Journal Article
- MeSH
- Acetylcholinesterase metabolism MeSH
- Administration, Oral MeSH
- Injections, Intramuscular MeSH
- Organ Specificity MeSH
- Oximes administration & dosage blood pharmacokinetics MeSH
- Area Under Curve MeSH
- Pyridinium Compounds administration & dosage blood pharmacokinetics MeSH
- Cholinesterase Reactivators administration & dosage blood pharmacokinetics MeSH
- Sus scrofa MeSH
- Tissue Distribution MeSH
- Chromatography, High Pressure Liquid MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
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; 1500mg/animal). According to the results, both oximes had similar Cmax (K027: 106±19μg/mL and K203: 111±8μg/mL) in Tmax 19±5min, respectively, in 22±3min. Bioavailability of oxime K027 calculated as AUCtotal (8389±1024minμg/mL) was halved compared to oxime K203 (16938±795minμg/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.
Biomedical Research Center University Hospital Hradec Kralove Czech Republic
Department of Military Surgery Faculty of Military Health Sciences Hradec Kralove Czech Republic
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc17030931
- 003
- CZ-PrNML
- 005
- 20171027103419.0
- 007
- ta
- 008
- 171025s2017 ne f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.toxlet.2017.03.017 $2 doi
- 035 __
- $a (PubMed)28343895
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a ne
- 100 1_
- $a Karasova, Jana Zdarova $u Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic; Biomedical Research Center, University Hospital, Hradec Kralove, Czech Republic. Electronic address: zdarova.jana@gmail.com.
- 245 10
- $a Pharmacokinetic profile of promising acetylcholinesterase reactivators K027 and K203 in experimental pigs / $c JZ. Karasova, J. Kvetina, I. Tacheci, V. Radochova, K. Musilek, K. Kuca, J. Bures,
- 520 9_
- $a 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; 1500mg/animal). According to the results, both oximes had similar Cmax (K027: 106±19μg/mL and K203: 111±8μg/mL) in Tmax 19±5min, respectively, in 22±3min. Bioavailability of oxime K027 calculated as AUCtotal (8389±1024minμg/mL) was halved compared to oxime K203 (16938±795minμg/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.
- 650 _2
- $a acetylcholinesterasa $x metabolismus $7 D000110
- 650 _2
- $a aplikace orální $7 D000284
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a plocha pod křivkou $7 D019540
- 650 _2
- $a reaktivátory cholinesterasy $x aplikace a dávkování $x krev $x farmakokinetika $7 D002801
- 650 _2
- $a vysokoúčinná kapalinová chromatografie $7 D002851
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a injekce intramuskulární $7 D007273
- 650 _2
- $a orgánová specificita $7 D009928
- 650 _2
- $a oximy $x aplikace a dávkování $x krev $x farmakokinetika $7 D010091
- 650 _2
- $a pyridinové sloučeniny $x aplikace a dávkování $x krev $x farmakokinetika $7 D011726
- 650 _2
- $a Sus scrofa $7 D034421
- 650 _2
- $a tkáňová distribuce $7 D014018
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Kvetina, Jaroslav $u 2nd Department of Medicine - Gastroenterology, Charles University Faculty of Medicine and University Hospital, Hradec Kralove, Czech Republic.
- 700 1_
- $a Tacheci, Ilja $u 2nd Department of Medicine - Gastroenterology, Charles University Faculty of Medicine and University Hospital, Hradec Kralove, Czech Republic.
- 700 1_
- $a Radochova, Vera $u Department of Military Surgery, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.
- 700 1_
- $a Musilek, Kamil $u Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic; Biomedical Research Center, University Hospital, Hradec Kralove, Czech Republic.
- 700 1_
- $a Kuca, Kamil $u Biomedical Research Center, University Hospital, Hradec Kralove, Czech Republic.
- 700 1_
- $a Bures, Jan $u 2nd Department of Medicine - Gastroenterology, Charles University Faculty of Medicine and University Hospital, Hradec Kralove, Czech Republic.
- 773 0_
- $w MED00004537 $t Toxicology letters $x 1879-3169 $g Roč. 273, č. - (2017), s. 20-25
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/28343895 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20171025 $b ABA008
- 991 __
- $a 20171027103504 $b ABA008
- 999 __
- $a ok $b bmc $g 1254524 $s 991958
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2017 $b 273 $c - $d 20-25 $e 20170323 $i 1879-3169 $m Toxicology letters $n Toxicol Lett $x MED00004537
- LZP __
- $a Pubmed-20171025
