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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Pickrell, JE; Hosaka, K; Jackson, DL; Heima, M; Kharasch, E; Milgrom, PM

Published Date

  • October 2009

Published In

Volume / Issue

  • 29 / 5

Start / End Page

  • 426 - 431

PubMed ID

  • 19745641

Pubmed Central ID

  • 19745641

Electronic International Standard Serial Number (EISSN)

  • 1533-712X

Digital Object Identifier (DOI)

  • 10.1097/JCP.0b013e3181b5f45e

Language

  • eng

Conference Location

  • United States