title: Pharmacokinetic effects of simultaneous administration of single-dose gabapentin 500 mg and zolpidem tartrate 10 mg in healthy volunteers: a randomized, open-label, crossover trial.
abstract: OBJECTIVE
  Gabapentin is being investigated as a potential treatment for occasional disturbed sleep. This study assessed the pharmacokinetics and tolerability of gabapentin 500 mg and the commonly prescribed sedative/hypnotic zolpidem tartrate 10 mg, administered separately and in combination.
  
  
  METHODS
  Forty healthy participants (19 male, 21 female) were randomized into this three-period crossover study [mean (range) age 34.1 (18-45) years, weight 68.3 (51.4-92.7) kg; 60 % white]. Participants were dosed with gabapentin alone (n = 39), zolpidem tartrate alone (n = 38), and the combination (gabapentin + zolpidem) (n = 38) over three treatment periods, which were separated by ≥7 days. Blood samples were collected pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24 and 36 h post-dose. Plasma concentrations of each drug were assayed using validated methods. Pharmacokinetic parameters were estimated from plasma concentration-time data using standard non-compartmental methods.
  
  
  RESULTS
  For gabapentin + zolpidem combination versus gabapentin alone, mean pharmacokinetic parameters were peak plasma concentration (C max) 4.61 versus 4.72 µg/mL, time to Cmax (t max) 4.63 versus 3.64 h and the area under plasma concentration-time curve extrapolated to infinity (AUC0-∞) 53.4 versus 51.0 µg h/mL. For the combination versus zolpidem alone, mean pharmacokinetic parameters were C max 154 versus 138 ng/mL, t max 1.45 versus 1.84 h and AUC0-∞ 912 versus 854 ng h/mL. The 90 % confidence intervals for C max (rate of absorption) and AUC0-∞ (extent of absorption) comparing the combination versus single drug administration fell within the 80-125 % range accepted for bioequivalence. All treatments were well tolerated.
  
  
  CONCLUSIONS
  The pharmacokinetics of gabapentin 500 mg and zolpidem tartrate 10 mg are unaffected when both drugs are taken simultaneously, compared with each drug taken alone.
authors.affiliation: Phase-1 Solutions, Miami Gardens, FL, USA.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Galitz
authors.forename: Shyamalie
authors.initials: S
authors.lastname: Jayawardena
authors.forename: Sandy A
authors.initials: SA
authors.lastname: Furey
mesh_terms: D000293:Adolescent; D000328:Adult; D000588:Amines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D000077206:Gabapentin; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D055815:Young Adult; D000077334:Zolpidem; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D006993:Hypnotics and Sedatives; D011725:Pyridines; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000077334:Zolpidem