title: Pharmacokinetics of zolpidem from sublingual zolpidem tartrate tablets in healthy elderly versus non-elderly subjects.
abstract: BACKGROUND
  Pharmacokinetic parameters of sedative-hypnotic medications can be influenced by age and gender.
  
  
  OBJECTIVE
  This study analyzed pharmacokinetic parameters of zolpidem, formulated as a sublingual zolpidem tartrate tablet (ZST; Intermezzo®), in healthy elderly males and females (mean age 72 years) and in non-elderly males and females (34 years).
  
  
  METHODS
  This was a randomized, single-dose, open-label, two-way crossover study evaluating pharmacokinetic parameters of 1.75 and 3.5 mg dosages of ZST in elderly subjects (n = 22), and 3.5 mg dosages of ZST in non-elderly subjects (n = 24). Main outcome measures were pharmacokinetic parameters, including area under the plasma concentration-time curve (AUC), maximum observed concentration (C(max)), time to reach C(max) (T(max)), elimination half-life (T(½)), and apparent oral clearance (CL/F).
  
  
  RESULTS
  Dose proportionality in zolpidem exposure was maintained between 1.75 and 3.5 mg doses for both elderly females and males. With administration of the 3.5 mg dose of ZST to elderly and non-elderly subjects, significantly higher systemic exposure was seen in elderly females (C(max) +44.6 %, P < 0.01; AUC +40.4 %) compared with non-elderly females. However, systemic exposure was only modestly higher in elderly males compared with non-elderly males. Greater exposure was seen in elderly females compared to males (C(max) +46.8 %, P < 0.01; AUC +31.4 %). In this study, exposure between non-elderly females and males was equivalent. Changes in T(½) and T(max) values were not observed, with no significant age effect on oral clearance. There were no apparent differences in tolerability among age and gender groups.
  
  
  CONCLUSIONS
  Elderly individuals were found to have higher C(max) and AUC values compared with non-elderly subjects. C(max) and AUC were greater in elderly women compared with elderly men.
authors.affiliation: Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, 136 Harrison Avenue, 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: Nikhilesh N
authors.initials: NN
authors.lastname: Singh
authors.forename: Frank
authors.initials: F
authors.lastname: Steinberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harris
authors.forename: Ram P
authors.initials: RP
authors.lastname: Kapil
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D000368:Aged; D000375:Aging; D019540:Area Under Curve; D018592:Cross-Over Studies; D005260:Female; D006299:Health Services for the Aged; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000077334:Zolpidem
chemical_list: D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem