Pharmacokinetics of two lorazepam formulations, oral and sublingual, after multiple doses

✍ Scribed by G. Caillé; J. Spénard; Y. Lacasse; J. Brennan

• Publisher: John Wiley and Sons
• Year: 1983
• Tongue: English
• Weight: 484 KB
• Volume: 4
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510040106

✦ Synopsis

The pharmacokinetic profiles of a sublingual and a conventional oral lorazepam tablet formulation were established following chronic administration to twelve healthy male volunteers. Fitting a multi-dose equation based on a one-compartment model to the observed data, the average elimination half-lives for the sublingual and oral doses are estimated to be 1 1 and 8 h, respectively, while the corresponding absorption half-lives are 15 and 55 min; this confirms earlier reports that the sublingual formulation is more rapidly absorbed.

The observed time to steady-state for both formulations was approximately 3 days, which agrees well with that predicted from previous single dosing studies. Although the sublingual formulation yields a higher average steady-state minimum plasma concentration than the oral formulation (41.6 versus 38.1 ngml-'), the maximum lorazepam concentration achieved during steady state was approximately 83 ng mlfor both formulations. The average steady-state plasma concentration is estimated to be 63 ng ml -', independent of the formulation used.