Toxogonin and Pralidoxime: Kinetic Comparison after Intravenous Administration to Man

Sidell, Frederick R.; Groff, William A.; Kaminskis, Andris

doi:10.1002/jps.2600611115

Cited by 49 publications

(24 citation statements)

References 7 publications

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“…9 peripheral compartment (V 2)' * In contrast, our data show significant changes in all those volumes (Table III). A definite explanation for this phenomenon is not possible, but the alternatives include: (I) increased protein binding affinity for oxime following thiamine administration (but since pralidoxime is negligibly bound, this seems unlikely); (2) increased sequestration of pralidoxime by other organs (e.g., central nervous system, liver); and (3) alteration of erythrocytic or vascular membrane permeabilities by as yet unknown mechanisms.…”

Section: Discussioncontrasting

confidence: 62%

“…A more detailed description of the derivation of this equation is provided by Wagner l3 and discussed with respect to pralidoxime in studies by Swartz and Sidell ll , 12 and Sidell, Groff, and Kaminskis. 9 The computer program NONLIN6 was used to estimate the parameters of this equation. From them the following were calculated:…”

Section: Methodsmentioning

confidence: 99%

“…1,4,5,9,11 This necessitates frequent administration in circumstances in which prolonged plasma concentration is desirable.…”

mentioning

confidence: 99%

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Effect of intravenous thiamine on pralidoxime kinetics

Josselson

Sidell

1978

Clin Pharma and Therapeutics

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Subjects were given pralidoxime chloride (5 mg/kg, intravenously) alone and again while they were receiving an infusion of thiamine hydrochloride. After the addition of thiamine: (1) overall, the urinary excretion of oxime was the same but the amount excreted in the first three hours was smaller; (2) the plasma half-life of oxime lengthened; (3) the plasma concentrations of oxime rose; and (4) the intercompartmental clearances and rate constant for elimination for oxime fell. These changes suggest that thiamine and oxime compete for a common renal secretory mechanism or that thiamine alters the membrane transport of oxime.

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Section: Discussioncontrasting

confidence: 62%

Section: Methodsmentioning

confidence: 99%

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Effect of intravenous thiamine on pralidoxime kinetics

Josselson

Sidell

1978

Clin Pharma and Therapeutics

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“…It can be concluded from that figure that, after the two initial doses of 500 mg, doses of 200 nag pralidoxime methylsulphate have to be repeated rather frequently to maintain plasma concentrations above 4 mg. 1-1, which is the usual expectedly therapeutic level Table 2. Pharmacokinetic data of pralidoxime methylsulphate in organophosphorus poisoned patients, compared with data obtained in healthy volunteers (Sidell et al 1972b (1): Infusion rate of 2.14 mg. kg -I 9 h -] (2): Double infusion rate (4): Quadruple infusion rate 9 : In these cases values were calculated on the basis of estimated weight, i.e. on the basis of an estimated dose rate Vdp is only calculated for the lower dose rate; the concentrations generated at that rate were of the same order of magnitude as the concentrations of the wash out curves used for the calculation of h/2 iO-mglt for oxime plasma concentrations (Sundwall 1961).…”

Section: Theoretical Simulationsmentioning

confidence: 99%

“…A continuous infusion has already been proposed for pralidoxime chloride therapy (Namba et al 1971;Thompson et al 1987;Farrar et al 1990). On the basis of the therapeutic level of 4 mg .1-1 and using mean pharmacokinetic data for pralidoxime methanesulphonate from healthy volunteers (Sidell et al 1972b), a loading dose of 4.42 mg.kg-1 and a maintenance dose of 2.14mg-kg-l.h-I can be calculated for pralidoxime methylsulphate (Willems and Belpaire 1991). The ensuing plasma concentration should then follow the time course given in Fig.…”

Section: Theoretical Simulationsmentioning

confidence: 99%

Plasma concentrations of pralidoxime methylsulphate in organophosphorus poisoned patients

Willems

Langenberg²,

Verstraete³

et al. 1992

Arch Toxicol

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Using pharmacokinetic data from healthy human volunteers in a bicompartmental pharmacokinetic model, a repeated dose scheme for pralidoxime methylsulphate (Contrathion) was developed producing plasma levels remaining above the assumed "therapeutic concentration" of 4 mg.l-1. Using the same data, it was found that a concentration of 4 mg.l-1 could also be obtained by a loading dose of 4.42 mg.kg-1 followed by a maintenance dose of 2.14 mg.kg-1.h-1. In order to study the pharmacokinetic behaviour of pralidoxime in poisoned patients, this continuous infusion scheme was then applied in nine cases of organophosphorus poisoning (agents: ethyl parathion, ethyl and methyl parathion, dimethoate and bromophos), and the pralidoxime plasma levels were determined. The mean plasma levels obtained in the various patients varied between 2.12 and 9 mg.l-1. Pharmacokinetic data were calculated, giving a total body clearance of 0.57 +/- 0.27 l.kg-1.h-1 (mean +/- SD), an elimination half-life of 3.44 +/- 0.90 h, and a volume of distribution of 2.77 +/- 1.45 l.kg-1.

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The pharmacokinetics of HI‐6 in beagle dogs

Simons

Briggs

1983

Biopharm & Drug Disp

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The pharmacokinetics of HI-6 were studied following intravenous administration to beagle dogs (n = 7). The bioavailability of two different strength intramuscularly administered doses was also determined in the same animals. After a 20 mg kg-1 intravenous dose, the mean (+/- S.D.) initial HI-6 plasma concentration was 93.1 +/- 10.8 micrograms ml-1. The mean half-life was 48.2 +/- 17.7 min, the mean total body clearance was 5.16 +/- 0.81 ml min-1 kg-1, the mean apparent volume of distribution was 0.37 +/- 0.20 l kg-1 and 61.2 +/- 14.6 per cent of the dose was excreted as unchanged drug. The pharmacokinetic constants calculated following the 20 mg kg-1 intramuscular doses of 250 and 25 mg ml-1 solutions were not significantly different from those obtained following the intravenous dose. Also, the areas under the plasma concentration versus time curves were not significantly different indicating 100 per cent bioavailability from the intramuscular route of administration.

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Toxogonin and Pralidoxime: Kinetic Comparison after Intravenous Administration to Man

Cited by 49 publications

References 7 publications

Effect of intravenous thiamine on pralidoxime kinetics

Effect of intravenous thiamine on pralidoxime kinetics

Plasma concentrations of pralidoxime methylsulphate in organophosphorus poisoned patients

The pharmacokinetics of HI‐6 in beagle dogs

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