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 (Cmax) 4.61 versus 4.72 µg/mL, time to Cmax (tmax) 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 Cmax 154 versus 138 ng/mL, tmax 1.45 versus 1.84 h and AUC0–∞ 912 versus 854 ng h/mL. The 90 % confidence intervals for Cmax (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.Conclusion: 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.