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Research Article

Pharmacokinetics Following a Loading Plus a Continuous Infusion of Pralidoxime Compared with the Traditional Short Infusion Regimen in Human Volunteers

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Pages 289-295 | Published online: 25 Sep 2008
 

Abstract

Background: Many authors currently recommend infusing the adult dose (1 g) of pralidoxime over a 15-30 minute period. When administered in this manner, computer simulations predict that plasma pralidoxime concentrations will fall below 4 mg/L as early as one and one half hours after administration.1 The objective of this study was to assess whether a loading dose followed by a continuous infusion would maintain therapeutic levels longer than the traditional short infusion regimen of pralidoxime if the same total dose was administered. Methods: Utilizing a randomized, crossover design, healthy volunteers were administered either 16 mg/kg of pralidoxime intravenous over 30 minutes or 4 mg/kg of pralidoxime intravenous over 15 minutes followed by 3.2 mg/kglhfor 3.75 h (for a total dose of 16 mg/kg). Pralidoxime levels were obtained at 0,10, 20, 30, 60, 120, 180, 240, 300, and 390 minutes and patients were observed for vital sign changes and adverse effects. Results: Seven subjects completed both arms of the study. One subject's data were excluded from pharmacokinetic analysis due to aberrant plasma pralidoxime analysis. The loading dose followed by the continuous infusion maintained therapeutic levels for 257.3 ± 50.5 minutes whereas the short infusion maintained therapeutic levels for 118.1 ± 52.1 (p < 0.001). Adverse effects were encountered during the short infusion regimen which did not occur during the continuous infusion. Dizziness or blurred vision occurred in all subjects during the short infusion regimen. Additionally, statistically significant increases in diastolic blood pressure occurred during the short infusion regimen. Conclusions: The results of this study indicate that a loading dose followed by a continuous infusion of pralidoxime maintains therapeutic concentrations for a longer period of time than the currently recommended short infusion regimen in healthy volunteers.

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