title: 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.
abstract: BACKGROUND
  A zolpidem sublingual tablet (ZST) formulation was recently approved by the US Food and Drug Administration to treat middle-of-the-night (MOTN) awakening with difficulty returning to sleep.
  
  
  OBJECTIVE
  The aim of this study was to compare the zolpidem pharmacokinetic profiles of 3.5-mg ZST and 10-mg immediate-release (IR) oral zolpidem in healthy female and male adults.
  
  
  METHODS
  This randomized, open-label crossover study compared the pharmacokinetic profile of ZST with that of IR oral zolpidem in healthy adults.
  
  
  RESULTS
  The study enrolled 19 males and 14 females. After 3.5-mg ZST and 10-mg IR, respectively, mean zolpidem plasma concentrations at 15 minutes (22 vs 17 ng/mL, respectively, in females and 18 vs 10 ng/mL in males) and AUCs from zero to 15 minutes (2.3 vs 0.8 ng · h/mL in females and 1.6 vs 0.5 ng · h/mL in males) were substantially greater for ZST, despite the larger absolute IR dose. After 3.5-mg ZST and 10-mg IR, respectively, clearance was lower in females, even after correcting for body weight (2.63 vs 2.88 mL/min/kg in females and 3.63 vs 3.91 mL/min/kg in males). The lag time prior to the start of first-order absorption was notably shorter for ZST than IR in both males (8 vs 21 minutes) and females (5 vs 22 minutes). Both zolpidem formulations were generally well tolerated by both genders.
  
  
  CONCLUSIONS
  Systemic exposure of zolpidem was higher in females for both formulations. Plasma levels and AUC were higher, and clearance was lower, in females with both zolpidem formulations. The initial rate of absorption was faster, and initial systemic exposure was greater, with ZST compared with oral IR.
authors.affiliation: Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, MA 02111, USA. dj.greenblatt@tufts.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Greenblatt
authors.forename: Jerold S
authors.initials: JS
authors.lastname: Harmatz
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
authors.forename: Nikhilesh N
authors.initials: NN
authors.lastname: Singh
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Moline
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harris
authors.forename: Ram P
authors.initials: RP
authors.lastname: Kapil
mesh_terms: D000284:Administration, Oral; D000286:Administration, Sublingual; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012737:Sex Factors; D013607:Tablets; D013997:Time Factors; D055815:Young Adult; D000077334:Zolpidem
chemical_list: D006993:Hypnotics and Sedatives; D011725:Pyridines; D013607:Tablets; D000077334:Zolpidem