The Pharmacokinetics of Continuous Infusion Pralidoxime in Children with Organophosphate Poisoning

Abstract

To define the pharmacokinetics of continuous infusion pralidoxime in organophosphate-poisoned children. Open-label study in 11 children and adolescents poisoned with organophosphates or carbamates. Serial blood samples were obtained during continuous pralidoxime infusion and after the drug was stopped. Patients were treated for 12-43 hours. Steady-state concentrations were (mean +/- SD) 22.2 +/- 12.3 mg/L. Volume of distribution ranged from 1.7 to 13.8 L/kg and was significantly higher in the more severely poisoned subjects. Elimination half-life was 3.6 +/- 0.8 hours, and clearance was 0.88 +/- 0.55 L/h/kg. After initiation of continuous infusion pralidoxime, only 1 patient required any additional atropine to control recurrent muscarinic symptoms. All patients exhibited complete clinical recovery. The pharmacokinetics of pralidoxime in poisoned children following continuous intravenous infusion are widely variable and differ from those previously reported in both healthy and poisoned adults. A loading dose of 25-50 mg/kg is recommended followed by a continuous infusion of 10-20 mg/kg/h. A loading dose of 50 mg/kg may be appropriate in more severely poisoned patients.