Abstract
Alprazolam immediate release (IR) tablets are currently approved for the management of anxiety disorder or the short-term relief of symptoms of anxiety. A sublingual (SL) formulation of alprazolam, which disintegrates in the mouth without the need for additional fluids, has been developed. The aim of this study was to determine if the alprazolam SL 1 mg tablet was bioequivalent to the alprazolam IR 1 mg tablet in healthy volunteers. In this randomized, open label, two-way crossover, single dose study, subjects were randomized to receive a single alprazolam 1 mg IR tablet during one dosing period and a single 1 mg SL tablet during the other dosing period. The primary pharmacokinetic endpoints were area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration AUC (0-t) and maximum plasma concentration (C max ). Adverse events (AEs) were monitored throughout the study. Bioequivalence was concluded if the 90% confidence intervals (CI) for the ratio of adjusted geometric means for both AUC (0-t) and C max were wholly within 80%-125%. Participants were mostly male (27/28 [96.4%]) and had a mean (standard deviation) age of 35.9 (8.2) years. For the alprazolam 1 mg SL tablet relative to the alprazolam 1 mg IR tablet, the ratio of adjusted geometric means (90% CI) for AUC (0-t) and C max were 95.43% (91.74%, 99.27%) and 88.27% (83.68%, 93.11%), respectively. The incidence of AEs was similar during both treatment periods: 24 participants reported 39 AEs during the alprazolam 1 mg IR treatment period, and 23 participants reported 38 AEs during the alprazolam 1 mg SL treatment period. Bioequivalence was demonstrated between the alprazolam IR and SL 1 mg tablets, suggesting that the clinical performance of the SL tablet will be similar to that of the IR tablet.
Highlights
The anxiolytic medication alprazolam, a 1,4 benzodiazepine compound, is indicated for the management of anxiety disorder or the short-term relief of symptoms of anxiety
Bioequivalence criteria were met for the alprazolam 1 mg SL formulation relative to the alprazolam 1 mg immediate release (IR) formulation as the corresponding 90% confidence intervals (CI) for the adjusted geometric mean AUCinf, AUC(0–t), and Cmax ratios were all contained within the 80% to 125% range
Bioequivalence criteria were met for the alprazolam 1 mg SL formulation with respect to both Cmax and AUC relative to the currently approved alprazolam 1 mg IR formulation
Summary
The anxiolytic medication alprazolam, a 1,4 benzodiazepine compound, is indicated for the management of anxiety disorder or the short-term relief of symptoms of anxiety. Alprazolam is indicated for the treatment of panic disorder, with or without agoraphobia [1]. Following oral administration of alprazolam immediate release (IR) tablets, alprazolam is readily absorbed, with peak concentrations in the plasma occurring between one and two hours following administration. Plasma levels are proportionate to the dose given: over the dose range of 0.5 to 3.0 mg, peak levels of 8.0 to 37 ng/mL were observed. The mean plasma elimination half-life (t1/2) of alprazolam has been found to be about 11.2 hours (range of 6.3 to 26.9 hours) in healthy adults [2,3,4]. Approximately 80% of alprazolam is bound to human serum protein, primarily serum albumin
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have