Comparison of intranasal administration of haloperidol with intravenous and intramuscular administration: A pilot pharmacokinetic study
Jodi L. Miller, J. Wesson Ashford, Sanford M. Archer, Anita C. Rudy, Daniel P. Wermeling
Study 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. Design. Randomized, open-label, three-way crossover study. Setting. Academic medical center. Subjects. Four healthy volunteers (two men, two women; aged 24-37 yrs). Intervention. 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). Measurements and Main 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-to-moderate nasal irritation after the intranasal doses. Conclusion. 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.
https://doi.org/10.1592/phco.28.7.875
Intranasal delivery
10.1592/phco.28.7.875
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Haloperidol Nursing and Health Professions 100%
Intranasal Drug Administration Nursing and Health Professions 77%
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Miller, J. L., Ashford, J. W., Archer, S. M., Rudy, A. C., & Wermeling, D. P. (2008). Comparison of intranasal administration of haloperidol with intravenous and intramuscular administration: A pilot pharmacokinetic study. Pharmacotherapy, 28(7), 875-882. https://doi.org/10.1592/phco.28.7.875
Miller, Jodi L. ; Ashford, J. Wesson ; Archer, Sanford M. et al. / Comparison of intranasal administration of haloperidol with intravenous and intramuscular administration : A pilot pharmacokinetic study. In: Pharmacotherapy. 2008 ; Vol. 28, No. 7. pp. 875-882.
@article{3feb8017fbbe44159c06c5026053e74a,
title = "Comparison of intranasal administration of haloperidol with intravenous and intramuscular administration: A pilot pharmacokinetic study",
abstract = "Study 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. Design. Randomized, open-label, three-way crossover study. Setting. Academic medical center. Subjects. Four healthy volunteers (two men, two women; aged 24-37 yrs). Intervention. 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). Measurements and Main 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-to-moderate nasal irritation after the intranasal doses. Conclusion. 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.",
keywords = "Antipsychotics, Drug delivery, Haloperidol, Intranasal delivery, Pharmacokinetics, Psychiatry",
author = "Miller, {Jodi L.} and Ashford, {J. Wesson} and Archer, {Sanford M.} and Rudy, {Anita C.} and Wermeling, {Daniel P.}",
doi = "10.1592/phco.28.7.875",
Miller, JL, Ashford, JW, Archer, SM, Rudy, AC & Wermeling, DP 2008, 'Comparison of intranasal administration of haloperidol with intravenous and intramuscular administration: A pilot pharmacokinetic study', Pharmacotherapy, vol. 28, no. 7, pp. 875-882. https://doi.org/10.1592/phco.28.7.875
Comparison of intranasal administration of haloperidol with intravenous and intramuscular administration : A pilot pharmacokinetic study. / Miller, Jodi L.; Ashford, J. Wesson; Archer, Sanford M. et al.
In: Pharmacotherapy, Vol. 28, No. 7, 07.2008, p. 875-882.
T1 - Comparison of intranasal administration of haloperidol with intravenous and intramuscular administration
T2 - A pilot pharmacokinetic study
AU - Miller, Jodi L.
AU - Ashford, J. Wesson
N2 - Study 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. Design. Randomized, open-label, three-way crossover study. Setting. Academic medical center. Subjects. Four healthy volunteers (two men, two women; aged 24-37 yrs). Intervention. 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). Measurements and Main 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-to-moderate nasal irritation after the intranasal doses. Conclusion. 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.
AB - Study 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. Design. Randomized, open-label, three-way crossover study. Setting. Academic medical center. Subjects. Four healthy volunteers (two men, two women; aged 24-37 yrs). Intervention. 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). Measurements and Main 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-to-moderate nasal irritation after the intranasal doses. Conclusion. 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.
KW - Antipsychotics
KW - Drug delivery
KW - Haloperidol
KW - Intranasal delivery
KW - Pharmacokinetics
KW - Psychiatry
U2 - 10.1592/phco.28.7.875
DO - 10.1592/phco.28.7.875
Miller JL, Ashford JW, Archer SM, Rudy AC, Wermeling DP. Comparison of intranasal administration of haloperidol with intravenous and intramuscular administration: A pilot pharmacokinetic study. Pharmacotherapy. 2008 Jul;28(7):875-882. doi: 10.1592/phco.28.7.875