Animal studies suggest that the minimum therapeutic concentration of pralidoxime in plasma is 4 µg/mL; this level is reached in about 16 minutes after a single injection of 600 mg pralidoxime chloride. In one study of healthy adult volunteers and patients self-poisoned with organophosphate compounds, a single intramuscular injection of 1000 mg of pralidoxime chloride resulted in mean peak plasma levels of 7.5 ± 1.7 µg/mL and 9.9 ± 2.4 µg/mL, respectively. Time to reach the mean peak plasma levels in both groups was similar, 34 minutes in healthy adults and 33 minutes in poisoned patients. Mean half-life was about 3 hours in both groups.

Some evidence suggests that a loading dose followed by continuous intravenous infusion of pralidoxime chloride may maintain therapeutic levels longer than short intermittent infusion therapy. In a cross-over study of seven healthy adults (18 – 50 years) a short intravenous infusion dose of 16 mg/kg over 30 minutes was compared to an intravenous loading dose of 4 mg/kg over 15 minutes, followed by 3.2 mg/kg/hr for 3.75 hours (for a total dose of 16 mg/kg). Results showed that the mean time over which plasma levels were maintained above 4 µg/mL was prolonged in the volunteers who received a loading dose followed by continuous infusion as compared to those who received short infusion therapy (257.5 ± 50.5 min vs. 118.0 ± 52.1 min). Use of continuous intravenous infusion in adult patients with organophosphate poisoning has been described in several case reports, with and without loading doses. Infusion rates ranged from 400 – 600 mg/hr. In one case the blood levels were 11.6 – 13.7 µg /mL when given 400 mg/hr over 5 days (measured at 5, 10 and 18 hours). In another case following an initial loading dose of 1000 mg, blood levels were 11.79 µg/mL when given 500 mg/hr and 17.26 µg/mL when given 600 mg/hr. In the latter case the pralidoxime elimination half-life was 4 hours. In two other cases blood levels were not measured.

Pralidoxime chloride is distributed throughout the extracellular water; its apparent volume of distribution at steady state has been reported to range from 0.60 to 2.7 L/kg. Pralidoxime chloride is not bound to plasma protein.

Pralidoxime chloride is relatively short acting and repeated doses may be needed, unless continuous intravenous infusion is selected. Simulations suggest that after a dose of 1000 mg given intravenously, concentrations fall below 4 µg/mL in about 1.5 hours. The short duration of action of pralidoxime chloride and the necessity for repeated doses should be considered especially where there is any evidence of continuing absorption of the poison. The apparent half-life of pralidoxime chloride is 74 to 77 minutes. The drug is rapidly excreted in the urine by renal tubular secretion, partly unchanged, and partly as a metabolite produced by the liver. After intramuscular administration of 1000 mg of pralidoxime chloride, the renal clearance has been reported to be 7.2 ± 2.9 mL/min/kg in healthy volunteers and 3.6 ± 1.5 mL/min/kg in organophosphate-poisoned patients.

In one study of 11 organophosphate-poisoned pediatric patients (age, 0.8 to 18 years), an intravenous loading dose of 15-50 mg/kg (mean 29 mg/kg) of pralidoxime chloride followed by a continuous infusion of 10-16 mg/kg/hr (mean 14 mg/kg/hr) over 12 to 43 hours (mean 27 ± 8 hours) resulted in an average steady state plasma concentration of 22.2 mg/L (6.9 to 47.4 mg/L) and an average body clearance of 0.88 L/kg/hr (0.28 to 2.20 L/kg/hr). After the continuous infusion was discontinued, determinations of the apparent volume of distribution and half-life ranged from 1.7 to 13.8 L/kg and from 2.4 to 5.3 hours, respectively.