Expanded Studies of the Pharmacokinetics and Clinical Effects of Multidose Sublingual Triazolam in Healthy Volunteers
| Autor: | Evan D. Kharasch, Kazuo Hosaka, Masahiro Heima, Peter Milgrom, Jacqueline E. Pickrell, Douglass L. Jackson |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Triazolam medicine.drug_class Sedation Administration Sublingual Conscious Sedation Cmax Pharmacology Placebo Article Sublingual administration Hypnotic Young Adult medicine Humans Pharmacology (medical) Dosing Dose-Response Relationship Drug business.industry Electroencephalography Psychiatry and Mental health Anesthesia Bispectral index Female medicine.symptom business medicine.drug |
| Zdroj: | Journal of Clinical Psychopharmacology. 29:426-431 |
| ISSN: | 0271-0749 |
| Popis: | Previous work described the pharmacokinetics and clinical effects of multidose sublingual triazolam (Halcion; PharmaciaUpjohn 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. |
| Databáze: | OpenAIRE |
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