Plasma concentrations of pralidoxime methylsulphate in organophosphorus poisoned patients.
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.
Willems
J L
JL
Heymans Institute of Pharmacology, University of Ghent Medical School, Belgium.
Langenberg
J P
JP
Verstraete
A G
AG
De Loose
M
M
Vanhaesebroeck
B
B
Goethals
G
G
Belpaire
F M
FM
Buylaert
W A
WA
Vogelaers
D
D
Colardyn
F
F
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
D007306:Insecticides; D009946:Organothiophosphorus Compounds; D011220:Pralidoxime Compounds; C028797:pralidoxime