title: Placebo-controlled comparative study of the anxiolytic activity and of the pharmacokinetics of oral and sublingual lorazepam in generalized anxiety.
abstract: In a randomized crossover study, twelve patients presenting a generalized anxiety disorder received either a 1 mg oral tablet or a 1 mg sublingual tablet of lorazepam three times daily for 7 days. After a 7-day washout period, each patient received a 7-day treatment with the other tablet form. Treatments were administered in a double-blind manner using placebos of both the oral and sublingual tablets. Psychiatric evaluations were carried out before and following each of the three periods. Blood samples were drawn at intervals for 48 h following the last dose of each treatment. The plasma concentrations of lorazepam were measured by gas chromatography using an electron-capture detector. Both the oral and sublingual lorazepam produced a significant anxiolytic effect; there was no statistically significant difference between the therapeutic effectiveness of the two forms of lorazepam. The main pharmacokinetic parameters for the oral and sublingual tablets were, respectively: elimination half-life 15.6h and 11.7h; maximal concentration 40.8 ng ml-1 and 42.2 ng ml-1; time to reach maximal concentration 1.2h and 1.4h; corrected area under the curve 310.6 ng hml-1 and 313.6 ng hml-1. There was no statistically significant difference between the oral and sublingual tablets for any of the pharmacokinetic parameters measured.
authors.affiliation: Département de pharmacologie, Faculté de médecine, Université de Montréal, Québec, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Spénard
authors.forename: G
authors.initials: G
authors.lastname: Caillé
authors.forename: C
authors.initials: C
authors.lastname: de Montigny
authors.forename: M
authors.initials: M
authors.lastname: Vézina
authors.forename: J
authors.initials: J
authors.lastname: Ouellette
authors.forename: L
authors.initials: L
authors.lastname: Larivière
authors.forename: F
authors.initials: F
authors.lastname: Trudel
mesh_terms: D000284:Administration, Oral; D000286:Administration, Sublingual; D000328:Adult; D001008:Anxiety Disorders / Q000097:blood / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D008140:Lorazepam / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D011897:Random Allocation
chemical_list: D008140:Lorazepam