title: 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.
authors.affiliation: Heymans Institute of Pharmacology, University of Ghent Medical School, Belgium.
authors.forename: J L
authors.initials: JL
authors.lastname: Willems
authors.forename: J P
authors.initials: JP
authors.lastname: Langenberg
authors.forename: A G
authors.initials: AG
authors.lastname: Verstraete
authors.forename: M
authors.initials: M
authors.lastname: De Loose
authors.forename: B
authors.initials: B
authors.lastname: Vanhaesebroeck
authors.forename: G
authors.initials: G
authors.lastname: Goethals
authors.forename: F M
authors.initials: FM
authors.lastname: Belpaire
authors.forename: W A
authors.initials: WA
authors.lastname: Buylaert
authors.forename: D
authors.initials: D
authors.lastname: Vogelaers
authors.forename: F
authors.initials: F
authors.lastname: Colardyn
mesh_terms: D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007306:Insecticides / Q000506:poisoning*; D008297:Male; D009946:Organothiophosphorus Compounds; D011041:Poisoning / Q000188:drug therapy; D011220:Pralidoxime Compounds / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D007306:Insecticides; D009946:Organothiophosphorus Compounds; D011220:Pralidoxime Compounds; C028797:pralidoxime