Comparison of pharmacokinetic profiles of zolpidem buffered sublingual tablet and zolpidem oral immediate-release tablet: results from a single-center, single-dose, randomized, open-label crossover study in healthy adults.
Level 2 - randomized trial
Single-center randomized crossover trial in healthy volunteers
PubMed 23541711 · doi:10.1016/j.clinthera.2013.03.007
What was done
A single-center, single-dose, randomized, open-label crossover pharmacokinetic study evaluated 33 healthy adults (19 males, 14 females). Participants received a 3.5-mg zolpidem sublingual tablet (ZST) and a 10-mg oral immediate-release (IR) zolpidem tablet to compare early plasma concentrations, early area under the curve (AUC 0–15 min), absorption lag time, and weight-corrected clearance stratified by sex.
What was found
Mean plasma concentration at 15 minutes for 3.5-mg ZST versus 10-mg IR was 22 vs 17 ng/mL in females and 18 vs 10 ng/mL in males. AUC from 0 to 15 minutes was 2.3 vs 0.8 ng·h/mL in females and 1.6 vs 0.5 ng·h/mL in males. Absorption lag time was shorter for ZST (5 vs 22 minutes in females; 8 vs 21 minutes in males). Weight-adjusted clearance was lower in females for both formulations (2.63 vs 2.88 mL/min/kg in females; 3.63 vs 3.91 mL/min/kg in males). Both treatments were generally well tolerated.
Why it matters
These findings show that low-dose sublingual zolpidem achieves more rapid initial systemic exposure than higher-dose oral zolpidem, supporting its suitability for middle-of-the-night awakenings, while reinforcing known sex differences in zolpidem metabolism.
Limits
The study was small (n=33), open-label, single-center, and conducted exclusively in healthy volunteers after single doses. It evaluated pharmacokinetic metrics rather than clinical sleep architecture, sleep latency endpoints, or next-day residual sedation.
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- context The lowest commercially available dose of standard immediate-release Ambien (zolpidem) is 5 mg.