Pharmacokinetics of two lorazepam formulations, oral and sublingual, after multiple doses.
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 11 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 ng ml-1), the maximum lorazepam concentration achieved during steady state was approximately 83 ng ml-1 for both formulations. The average steady-state plasma concentration is estimated to be 63 ng ml-1, independent of the formulation used.
D000284:Administration, Oral; D000328:Adult; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008140:Lorazepam / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D014059:Tongue
D014151:Anti-Anxiety Agents; D008140:Lorazepam