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

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 C_max (t_max) 4.63 versus 3.64 h and the area under plasma concentration–time curve extrapolated to infinity (AUC_0–∞) 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 AUC_0–∞ 912 versus 854 ng h/mL. The 90 % confidence intervals for C_max (rate of absorption) and AUC_0–∞ (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.     

The prevalence,predictors and associations of hypertension in Sri Lanka: a cross-sectional population based national survey

We studied the community prevalence, patterns and predictors of hypertension in a large sub-population of South Asian adults with a view of identifying differential risk factors. Data were collected between years 2005–2006 and 5000 adults were invited for the study. The sample size was 4485, and about 39.5% were males. Mean systolic and diastolic blood pressures were 127.1?±?19.8?mmHg and 75.4?±?11.3?mmHg, respectively. Age-adjusted prevalence in all adults, males and females was 23.7%, 23.4% and 23.8%, respectively. Urban adults had a significantly higher prevalence of hypertension than rural adults. In the binary logistic–regression analysis, male gender (OR: 1.2), increasing age, Sri Lankan Moor ethnicity (OR: 1.6), physical inactivity (OR: 1.7), presence of diabetes (OR: 2.2) and central obesity (OR: 2.3) all were significantly associated with hypertension. In conclusion, nearly one-third of the Sri Lankan adult population is hypertensive. Hence, public health initiatives should encourage healthier lifestyles with emphasis on preventing obesity and increasing physical activity.