Plasma concentrations of pralidoxime methylsulphate in organophosphorus poisoned patients

Abstract

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.

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

“…Furthermore, the relationship between oximes plasma concentration and protection against organophosphate poisoning is not well defined [10]. According to some studies [7,13], a plasma concentration at or above 4 mg L −1 is required to observe a therapeutic efficacy. Due to its rapid renal excretion, various administration protocols have been tested in man to achieve this therapeutic range [7,8,14].…”

“…According to some studies [7,13], a plasma concentration at or above 4 mg L −1 is required to observe a therapeutic efficacy. Due to its rapid renal excretion, various administration protocols have been tested in man to achieve this therapeutic range [7,8,14]. In these studies, pralidoxime plasma concentrations were determined, but pharmacokinetic param- eters were calculated only in few cases of human poisoning [7].…”

“…1) or as chloride salts (Protopam ® ) [6]. Despite human [7][8][9] and animal studies [10,11], the usefulness of pralidoxime therapy is still questioned. Treatment by oximes is not always successful due to differing toxicological activity among OP compounds, delays between poisoning and treatment, "ageing" of the compound at the receptor, lack of central action and absence of standardized therapeutic infusion schemes [12].…”

Cholinesterase reactivation in organophosphorus poisoned patients depends on the plasma concentrations of the oxime pralidoxime methylsulphate and of the organophosphate

“…It is, however, not known which plasma concentrations are generated by these different schemes in poisoned patients. Neither is it known what plasma concentrations are needed, and for how long, to counteract the possible long persistence of the cholinesterase inhibitor in the body (for references see Willems et al 1992).…”

Measurement of TS-131, a New Monopyridinium Oxime, by High Performance Liquid Chromatography in Rat Plasma Samples

“…The available oximes have been quantitatively determined using high performance liquid chromatography (HPLC). Using this technique, it was possible to monitor the blood concentration and urinary elimination of pralidoxime [16][17][18][19][20][21][22]. Urinary elimination of obidoxime was followed by reversed-phase chromatography.…”