title: Pharmacokinetics following a loading plus a continuous infusion of pralidoxime compared with the traditional short infusion regimen in human volunteers.
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. 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/kg/h for 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.
authors.affiliation: University Hospital, State University of New York, Health Science Center at Syracuse 13210, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Medicis
authors.forename: C M
authors.initials: CM
authors.lastname: Stork
authors.forename: M A
authors.initials: MA
authors.lastname: Howland
authors.forename: R S
authors.initials: RS
authors.lastname: Hoffman
authors.forename: L R
authors.initials: LR
authors.lastname: Goldfrank
mesh_terms: D000328:Adult; D000931:Antidotes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011220:Pralidoxime Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012016:Reference Values
chemical_list: D000931:Antidotes; D011220:Pralidoxime Compounds; C028797:pralidoxime