Acute renal failure alters the kinetics of pralidoxime in rats.
There is a trend towards increasing doses of pralidoxime to treat human organophosphate poisonings that may have relevance in subpopulations. Indeed, pralidoxime is eliminated unchanged by the renal route. This study assesses the effect of renal failure on the kinetics of pralidoxime in a rat model of acute renal failure induced by potassium dichromate administration. On the first day, Sprague-Dawley rats received subcutaneously potassium dichromate (study) or saline (control). Forty-eight hours post-injection, animals received pralidoxime methylsulfate (50mg/kg of pralidoxime base) intramuscularly. Blood specimens were sampled during 180min after the injection. Urine was collected daily during the 3 days of the study. Plasma pralidoxime concentrations were measured by liquid chromatography with electrochemical detection. There was a 2-fold increase in mean elimination half-life and a 2.5-fold increase in mean area under the curve in the study compared to the control group. The mean total body clearance was halved in the study compared to the control group. Our study showed acute renal failure does not modify the distribution of pralidoxime but significantly alters its elimination from plasma. These results suggest that dosages of pralidoxime should be adjusted in organophosphate-poisoned humans with renal failure when using high dosage regimen of pralidoxime.
Kayouka
Maya
M
Université Paris Descartes, faculté de Pharmacie, Neuropsychopharmacologie des addictions, CNRS, UMR7157 et Université Paris 7, Paris F-75010, France; INSERM, U705, Paris F-75010, France. maya.kayouka@gmail.com
Houzé
Pascal
P
Risède
Patricia
P
Debray
Marcel
M
Baud
Frederic J
FJ
D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D000931:Antidotes / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002853:Chromatography, Liquid; D006207:Half-Life; D008297:Male; D008657:Metabolic Clearance Rate; D011220:Pralidoxime Compounds / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000931:Antidotes; D011220:Pralidoxime Compounds; C028797:pralidoxime