Sublingual administration of alprazolam: a pharmacokinetic approach

Abstract

A rapid onset of drug action is desirable for patients experiencing panic attacks or episodes of acute anxiety. The aim of this single-dose, three-sequence, crossover study was to investigate the pharmacokinetics of the anxiolytic alprazolam after administration of a single 0.5 mg dose of the drug, in tablets designed for sublingual administration (Tranquinal sublingual; Laboratorios Bago, test product, Ts) compared with oral (Ro) and sublingual (Rs) administration of 0.5 mg of alprazolam of a reference product (Xanax; Pharmacia Upjohn) manufactured for standard oral administration. Blood samples were taken at 0 (before) and 4, 6, 8, 10, 12, 15, 20, 30, 45, 60, 120, 180 and 240 min and 30 h after drug administration, and plasma concentrations of alprazolam were determined by high performance liquid chromatography. The area under the time-concentration curve (AUC) over 0 to 15 min (ng ml−1 hr−1) was 0.12±0.03 for Ts, 0.07±0.03 for Ro and 0.05±0.02 for Rs (P<0.05). The AUC0–4 h values were 22.09±1.96; 22.50±0.99 and 19.65±0.95 for Ts, Ro and R s, respectively, and the AUC0–30 h values were 109.05±12.21, 121.30±4.82 and 111.28±4.87 for Ts, Ro and Rs, respectively. C max values were 6.79±0.85, 7.11±0.64 and 6.14±0.30 ng/ml for Ts, Ro and Rs, respectively, whereas the Tmax was 2 h for all three. The results suggest that measurable plasma concentrations of the sublingual test product are achieved more rapidly than with oral or sublingual administration of a standard reference preparation of alprazolam, which might have therapeutic advantages.