Sarin intoxication elevates plasma pralidoxime

Green, Martin D.; Jones, Dennis E.; Hilmas, Duane E.

doi:10.1016/0378-4274(85)90004-9

Cited by 17 publications

(1 citation statement)

References 10 publications

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“…It has been reported that administration of OP nerve agents can alter the elimination kinetics of 2-PAM (Green et al 1985a). The administration of sarin or soman caused a biphasic response in the maximal plasma concentration of 2-PAM.…”

Section: Discussionmentioning

confidence: 98%

In vivooxime administration does not influence Ellman acetylcholinesterase assay results

Guarisco¹,

O‘Donnell²,

Skovira³

et al. 2009

Toxicology Mechanisms and Methods

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Organophosphorus compounds (OPs) are potent inhibitors of acetylcholinesterase (AChE). Treatment for OP poisoning is by administration of atropine sulfate, an oxime, and diazepam. Oximes such as 2-PAM are used to reactivate OP-inhibited AChE so as to restore normal enzymatic function and serve as a true antidote. There are reports of non-enzymatic hydrolysis by oximes of acetylthiocholine in in vitro preparations in the widely used Ellman assay for AChE activity, which may confound the interpretation of AChE activity by producing elevated results. The purpose of this experiment was to determine if there is appreciable interference by therapeutic levels of oximes on the results of the Ellman assay in assessing AChE reactivation by oxime compounds in vivo. When therapeutic doses of oximes (2-PAM, HI-6, MMB-4, or MINA) were administered intramuscularly to guinea pigs and samples collected 60 min later, there was no statistical difference between oxime and saline control groups in measured AChE activity in various tissue samples, including blood. With appropriate dilution of samples prior to spectrophotometric assay, the Ellman assay is an acceptable method to measure in vivo oxime reactivation of inhibited AChE. Inclusion of an oxime control group to insure that this particular type of interference is not causing false readings in the assay is a prudent step.

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Section: Discussionmentioning

confidence: 98%

In vivooxime administration does not influence Ellman acetylcholinesterase assay results

Guarisco¹,

O‘Donnell²,

Skovira³

et al. 2009

Toxicology Mechanisms and Methods

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Effect of poisoning by soman (pinacolyl methylphosphono‐fluoridate) on the serum half‐life of the cholinesterase reactivator hi‐6 in mice

Clement¹,

Simons

Briggs³

1988

Biopharm & Drug Disp

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The effect of fasting, atropine, and poisoning by an organophosphate anticholinesterase soman (pinacolyl methylphosphonofluoridate) on the pharmacokinetics of the acetylcholinesterase oxime reactivator HI-6 (CAS Reg. No. 34433-31-3; 1-[(4-(aminocarbonyl)pyridinio)methoxy)methyl)-2-(hydroxy imino)methyl) pyridinium dichloride) was investigated. Pharmacokinetic parameters (elimination half-life, volume of distribution, clearance rate) were determined for the following groups: (1) a 20 and 50 mg kg-1 dose of HI-6; (2) a 50 mg kg-1 dose of HI-6 after fasting for 18 h (water ad lib); (3) a 50 mg kg-1 dose of HI-6 at 0, 4, and 24 h after atropine (17.4 mg kg-1, i.p.) and soman (287 micrograms kg-1, s.c.); and (4) a 50 mg kg-1 dose of HI-6 at 0 and 4 h after soman (100 micrograms kg-1, s.c.). Fasting increased significantly (p less than 0.05) the elimination of half-life (t1/2) and tended to increase the volume of distribution (Vd) and decrease the clearance rate (CL). Following soman (287 micrograms kg-1) poisoning the t1/2 of HI-6 increased from 8.6 min to 21.6 min and the Vd increased to 0.731 kg-1. At the lower soman dose (100 micrograms kg-1) no significant effect on HI-6 pharmacokinetics was found. Atropine (17.4 mg kg-1: i.p.) pretreatment increased the t1/2 and CL while having no effect on the Vd. By 24 h the pharmacokinetic parameters of HI-6 in the various treatment groups were not significantly different from the control group. The changes in the pharmacokinetics of HI-6 following soman and atropine are probably the result of haemodynamic changes.

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Oximes

Vale¹

2017

Critical Care Toxicology

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Sarin intoxication elevates plasma pralidoxime

Cited by 17 publications

References 10 publications

In vivooxime administration does not influence Ellman acetylcholinesterase assay results

In vivooxime administration does not influence Ellman acetylcholinesterase assay results

Effect of poisoning by soman (pinacolyl methylphosphono‐fluoridate) on the serum half‐life of the cholinesterase reactivator hi‐6 in mice

Oximes

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