Daytime pharmacodynamic and pharmacokinetic evaluation of low-dose sublingual transmucosal zolpidem hemitartrate.
OBJECTIVE
Buffered low-dose sublingual transmucosal zolpidem lozenge hemitartrate (ST zolpidem) is being developed for the treatment of middle-of-the-night insomnia. The objective of this double-blind placebo-controlled cross-over study (n = 24) was to evaluate the pharmacokinetics (PK) and daytime-sedative profile of 1.0, 1.75, and 3.5 mg dose of the formulation.


METHODS
Daytime sedation was measured pre-dose and up to 5 h post-dose objectively by the Digit Symbol Substitution Test (DSST) and subjectively using the Visual Analog Scale (VAS). Blood samples for PK assessment was collected pre-dose and up to 12 h post-dose.


RESULTS
The 1.75 and 3.5 mg, but not the 1 mg, ST zolpidem produced significant sedation versus placebo within 20 min of dosing which lasted for up to 3 h. Zolpidem from the formulation was rapidly absorbed and reached maximum plasma concentrations within 38 min of dosing, however the half-life was independent of the dose and side effects were consistent with the known pharmacology of the drug.


CONCLUSIONS
ST zolpidem produced rapid, short duration of sedation and the effect was consistent with its PK profile. This novel low-dose formulation of zolpidem may provide clinicians and patients with a prn option for the management of sleep maintenance insomnia.
Roth
Thomas
T
Henry Ford Hospital, Sleep Disorders and Research Center, Detroit, MI 48202, USA. troth1@hfhs.org
Mayleben
David
D
Corser
Bruce C
BC
Singh
Nikhilesh N
NN
D000286:Administration, Sublingual; D000328:Adult; D000704:Analysis of Variance; D002940:Circadian Rhythm / Q000187:drug effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D010147:Pain Measurement; D011597:Psychomotor Performance / Q000187:drug effects; D011725:Pyridines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013997:Time Factors; D000077334:Zolpidem
D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem