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Expanded studies of the pharmacokinetics and clinical effects of multidose sublingual triazolam in healthy volunteers.

Publication ,  Journal Article
Pickrell, JE; Hosaka, K; Jackson, DL; Heima, M; Kharasch, E; Milgrom, PM
Published in: J Clin Psychopharmacol
October 2009

Previous work described the pharmacokinetics and clinical effects of multidose sublingual triazolam (Halcion; Pharmacia & Upjohn Co, Kalamazoo, Mich). This laboratory study evaluated the hypothesis that incremental dosing of triazolam produces dose-dependent central nervous system depression that is profound and long lasting. Forty-nine healthy adults between the ages of 21 and 39 years, not receiving dental treatment, were randomly assigned to placebo (n = 12) or 1 of 3 triazolam groups (0.25-mg single dose, n = 12; 0.5 mg divided between 2 equal doses for 60 minutes, n = 12; or 0.75 mg divided among 3 doses for 90 minutes, n = 13). Plasma triazolam concentrations were determined. Bispectral index (BIS) and the Observer Assessment of Alertness/Sedation scale were used to assess sedation. Plasma triazolam concentrations increased with time in all subjects, with Tmax and Cmax both increasing dose dependently. Compared with placebo, all dosing paradigms produced dose-dependent BIS suppression and sedation. The single dose of 0.25 mg reached its peak BIS suppression at 90 (81 +/- 7) minutes and sedation at 120 (3.6 +/- 0.5) minutes and returned to baseline before 360 minutes. In contrast, incremental dosing of 0.5 and 0.75 mg produced profound and long-lasting BIS suppression and sedation that did not plateau until either 180 or 210 minutes as measured by the BIS index (67 +/- 14 and 60 +/- 16 at 0.5 and 0.75 mg, respectively) and 150 minutes as measured by the Observer Assessment of Alertness/Sedation scale (3.2 +/- 1.0 and 2.7 +/- 0.4 at 0.5 and 0.75 mg, respectively). These data more fully characterize the effects of incremental dosing with sublingual triazolam and provide additional insight for discharge safety recommendations.

Duke Scholars

Published In

J Clin Psychopharmacol

DOI

EISSN

1533-712X

Publication Date

October 2009

Volume

29

Issue

5

Start / End Page

426 / 431

Location

United States

Related Subject Headings

  • Young Adult
  • Triazolam
  • Psychiatry
  • Male
  • Humans
  • Female
  • Electroencephalography
  • Dose-Response Relationship, Drug
  • Conscious Sedation
  • Adult
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Pickrell, J. E., Hosaka, K., Jackson, D. L., Heima, M., Kharasch, E., & Milgrom, P. M. (2009). Expanded studies of the pharmacokinetics and clinical effects of multidose sublingual triazolam in healthy volunteers. J Clin Psychopharmacol, 29(5), 426–431. https://doi.org/10.1097/JCP.0b013e3181b5f45e
Pickrell, Jacqueline E., Kazuo Hosaka, Douglass L. Jackson, Masahiro Heima, Evan Kharasch, and Peter M. Milgrom. “Expanded studies of the pharmacokinetics and clinical effects of multidose sublingual triazolam in healthy volunteers.J Clin Psychopharmacol 29, no. 5 (October 2009): 426–31. https://doi.org/10.1097/JCP.0b013e3181b5f45e.
Pickrell JE, Hosaka K, Jackson DL, Heima M, Kharasch E, Milgrom PM. Expanded studies of the pharmacokinetics and clinical effects of multidose sublingual triazolam in healthy volunteers. J Clin Psychopharmacol. 2009 Oct;29(5):426–31.
Pickrell, Jacqueline E., et al. “Expanded studies of the pharmacokinetics and clinical effects of multidose sublingual triazolam in healthy volunteers.J Clin Psychopharmacol, vol. 29, no. 5, Oct. 2009, pp. 426–31. Pubmed, doi:10.1097/JCP.0b013e3181b5f45e.
Pickrell JE, Hosaka K, Jackson DL, Heima M, Kharasch E, Milgrom PM. Expanded studies of the pharmacokinetics and clinical effects of multidose sublingual triazolam in healthy volunteers. J Clin Psychopharmacol. 2009 Oct;29(5):426–431.

Published In

J Clin Psychopharmacol

DOI

EISSN

1533-712X

Publication Date

October 2009

Volume

29

Issue

5

Start / End Page

426 / 431

Location

United States

Related Subject Headings

  • Young Adult
  • Triazolam
  • Psychiatry
  • Male
  • Humans
  • Female
  • Electroencephalography
  • Dose-Response Relationship, Drug
  • Conscious Sedation
  • Adult