title: Comparison of intranasal administration of haloperidol with intravenous and intramuscular administration: a pilot pharmacokinetic study.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics of haloperidol after intranasal administration compared with intravenous and intramuscular administration, and to evaluate systemic and local tolerance of intranasal administration.
  
  
  METHODS
  Randomized, open-label, three-way crossover study.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  Four healthy volunteers (two men, two women; aged 24-37 yrs).
  
  
  METHODS
  Each subject received in a randomized order the following three treatments, with a 2-week washout period between treatments: intravenous haloperidol 2.5 mg (0.5 ml of 5.0 mg/ml) infused over 15 minutes, intramuscular haloperidol 2.5 mg (0.5 ml of 5.0 mg/ml), and intranasal haloperidol 2.5 mg (2.5 mg/0.1-ml spray into a single naris).
  
  
  RESULTS
  Blood samples were obtained serially and plasma levels determined. Noncompartmental analysis was used to estimate pharmacokinetic parameters. Physical and nasal examinations and adverse-effect profiles were obtained to assess tolerance. Mean (percent coefficient of variation) haloperidol bioavailability after intranasal administration was 63.8% (24.4%) compared with intravenous administration and 48.6% (29.4%) compared with intramuscular administration. Intranasal administration achieved higher peak levels that occurred more quickly compared with intramuscular administration. Median time to maximum concentration was 15 minutes after the intranasal dose compared with 37.5 and 15 minutes after the intramuscular and intravenous doses, respectively. Subjects had mild-to-moderate systemic adverse effects, all related to an extension of haloperidol's pharmacologic actions. Two of the four subjects complained of mild-tomoderate nasal irritation after the intranasal doses.
  
  
  CONCLUSIONS
  Our results suggest that additional research studies are warranted for further evaluation of intranasal administration of haloperidol. The product provides rapid therapeutic plasma levels and sedation, with only minor and short-lived nasal irritation. These data suggest that intranasal administration of haloperidol, or other antipsychotics with similar potency, could play a role in treating psychiatric emergencies.
authors.affiliation: Solvay Pharmaceuticals, Inc., Marietta, Georgia, USA.
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Miller
authors.forename: J Wesson
authors.initials: JW
authors.lastname: Ashford
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Archer
authors.forename: Anita C
authors.initials: AC
authors.lastname: Rudy
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Wermeling
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male
chemical_list: D014150:Antipsychotic Agents; D006220:Haloperidol