Toxogonin: Blood Levels and Side Effects After Intramuscular Administration In Man

Sidell, Frederick R.; Groff, William A.

doi:10.1002/jps.2600590615

Cited by 49 publications

(15 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The excreted amount in urine accounted for 88-100% of the administered dose. These values are higher than those reported after intravenous [25] or intramuscular injections [26]. In two samples and after modifications of pralidoxime infusion regimen, excreted amounts in urine were greater than infused quantities.…”

Section: Clinical Applicationcontrasting

confidence: 51%

Measurement of serum pralidoxime methylsulfate (Contrathion®) by high-performance liquid chromatography with electrochemical detection

Houzé

Borron

Scherninski³

et al. 2005

Journal of Chromatography B

View full text Add to dashboard Cite

Section: Clinical Applicationcontrasting

confidence: 51%

Measurement of serum pralidoxime methylsulfate (Contrathion®) by high-performance liquid chromatography with electrochemical detection

Houzé

Borron

Scherninski³

et al. 2005

Journal of Chromatography B

View full text Add to dashboard Cite

“…An initial oxime concentration of 30 μM was selected since pharmacokinetic data in humans indicate a peak plasma concentration of i.m. HI 6 (500 mg) and obidoxime (220 mg) in the range 30-40 μM (Clement et al, 1995;Sidell and Groff, 1970). Such oxime doses are presently used in autoinjectors (Szinicz and Kullmann, 1990;Clement et al, 1995).…”

Section: Discussionmentioning

confidence: 98%

Reactivation of organophosphate‐inhibited human AChE by combinations of obidoxime and HI 6 in vitro

Worek

Aurbek

Thiermann

2007

J of Applied Toxicology

View full text Add to dashboard Cite

Highly toxic organophosphorus-type (OP) chemical warfare agents (nerve agents) and OP pesticides may be used by terrorists and during military conflicts emphasizing the necessity for the development of effective medical countermeasures. The standard treatment with atropine and acetylcholinesterase (AChE) reactivators (oximes) is considered to be ineffective with certain nerve agents due to low oxime efficacy. Despite research over decades none of the oximes has turned out to be a broad spectrum reactivator to cover the whole range of potential threat agents. The prospective oxime HI 6 is a weak reactivator of tabun- and pesticide-inhibited AChE, while the established oxime obidoxime mainly lacks efficacy with cyclosarin-inhibited enzyme. In order to investigate the feasibility of combining obidoxime and HI 6, human AChE inhibited by sarin, cyclosarin, VX, tabun and paraoxon was reactivated by these oximes either alone or in combination. Two major findings of this study were that a combination of HI 6 and obidoxime did not impair reactivation, compared with HI 6 or obidoxime alone, but broadened the spectrum compared with the individual oximes. By using different oxime concentrations a combination of oxime doses may be suggested which could be an alternative to individual obidoxime or HI 6 autoinjectors.

show abstract

“…We added the oximes obidoxime and HI-6 in concentrations of 50 µM to our model-a concentration comparable to the C max after intramuscular injection of 250 mg obidoxime and 500 mg HI-6 in humans (Sidell and Groff 1970;Clement et al 1995). Both oximes are supposed to turn ChE into a pseudocatalytic scavenger thus elevating the endogenous scavenging capacity to steadily decrease the VX load in the body.…”

Section: Discussionmentioning

confidence: 99%

Pseudocatalytic scavenging of the nerve agent VX with human blood components and the oximes obidoxime and HI-6

et al. 2016

View full text Add to dashboard Cite

Despite six decades of extensive research in medical countermeasures against nerve agent poisoning, a broad spectrum acetylcholinesterase (AChE) reactivator is not yet available. One current approach is directed toward synthesizing oximes with high affinity and reactivatability toward butyrylcholinesterase (BChE) in plasma to generate an effective pseudocatalytic scavenger. An interim solution could be the administration of external AChE or BChE from blood products to augment pseudocatalytic scavenging with slower but clinically approved oximes to decrease nerve agent concentrations in the body. We here semiquantitatively investigate the ability of obidoxime and HI-6 to decrease the inhibitory activity of VX with human AChE and BChE from whole blood, erythrocyte membranes, erythrocytes, plasma, clinically available fresh frozen plasma and packed red blood cells. The main findings are that whole blood showed a VX concentration-dependent decrease in inhibitory activity with HI-6 being more potent than obidoxime. Using erythrocytes and erythrocyte membranes again, HI-6 was more potent compared to obidoxime. With freshly prepared plasma, obidoxime and HI-6 showed comparable results for the decrease in VX. The use of the clinically available blood products revealed that packed red blood cells showed similar kinetics as fresh erythrocytes. Fresh frozen plasma resulted in a slower and incomplete decrease in inhibitory plasma compared to freshly prepared plasma. In conclusion, the administration of blood products in combination with available oximes augments pseudocatalytic scavenging and might be useful to decrease the body load of persistent, highly toxic nerve agents.

show abstract

Toxogonin: Blood Levels and Side Effects After Intramuscular Administration In Man

Cited by 49 publications

References 11 publications

Measurement of serum pralidoxime methylsulfate (Contrathion®) by high-performance liquid chromatography with electrochemical detection

Measurement of serum pralidoxime methylsulfate (Contrathion®) by high-performance liquid chromatography with electrochemical detection

Reactivation of organophosphate‐inhibited human AChE by combinations of obidoxime and HI 6 in vitro

Pseudocatalytic scavenging of the nerve agent VX with human blood components and the oximes obidoxime and HI-6

Contact Info

Product

Resources

About