Zolpidem 10 mg · Tablets

Zolpidem is a GABA A receptor positive modulator presumed to exert its therapeutic effects in the short-term treatment of insomnia through binding to the benzodiazepine site of α1 subunit containing GABA A receptors, increasing the frequency of chloride channel opening resulting in the inhibition of neuronal excitation.

The pharmacokinetic profile of zolpidem tartrate tablets is characterized by rapid absorption from the gastrointestinal tract and a short elimination half-life (T 1/2) in healthy subjects.

In a single-dose crossover study in 45 healthy subjects administered 5 and 10 mg zolpidem tartrate tablets, the mean peak concentrations (C max) were 59 (range: 29 to 113) and 121 (range: 58 to 272) ng/mL, respectively, occurring at a mean time (T max) of 1.6 hours for both. The mean zolpidem tartrate tablets elimination half-life was 2.6 (range: 1.4 to 4.5) and 2.5 (range: 1.4 to 3.8) hours, for the 5 and 10 mg tablets, respectively. Zolpidem tartrate tablets are converted to inactive metabolites that are eliminated primarily by renal excretion. Zolpidem tartrate tablets demonstrated linear kinetics in the dose range of 5 to 20 mg. Total protein binding was found to be 92.5 ± 0.1% and remained constant, independent of concentration between 40 and 790 ng/mL. Zolpidem did not accumulate in young adults following nightly dosing with 20 mg zolpidem tartrate tablets for 2 weeks.

A food-effect study in 30 healthy male subjects compared the pharmacokinetics of zolpidem tartrate tablets 10 mg when administered while fasting or 20 minutes after a meal. Results demonstrated that with food, mean AUC and C max were decreased by 15% and 25%, respectively, while mean T max was prolonged by 60% (from 1.4 to 2.2 hr). The half-life remained unchanged. These results suggest that, for faster sleep onset, zolpidem tartrate tablets should not be administered with or immediately after a meal.

Elderly — In the elderly, the dose for zolpidem tartrate tablets should be 5 mg [see Warnings and Precautions ( 5), Dosage and Administration ( 2)]. This recommendation is based on several studies in which the mean C max, T 1/2, and AUC were significantly increased when compared to results in young adults. In one study of eight elderly subjects (>70 years), the means for C max, T 1/2, and AUC significantly increased by 50% (255 vs. 384 ng/mL), 32% (2.2 vs. 2.9 hr), and 64% (955 vs. 1,562 ng·hr/mL), respectively, as compared to younger adults (20 to 40 years) following a single 20 mg oral dose. Zolpidem tartrate tablets did not accumulate in elderly subjects following nightly oral dosing of 10 mg for 1 week.

Hepatic Impairment — The pharmacokinetics of zolpidem tartrate tablets in eight patients with chronic hepatic insufficiency was compared to results in healthy subjects. Following a single 20 mg oral zolpidem tartrate dose, mean C max and AUC were found to be two times (250 vs. 499 ng/mL) and five times (788 vs. 4,203 ng·hr/mL) higher, respectively, in hepatically compromised patients. T max did not change. The mean half-life in cirrhotic patients of 9.9 hr (range: 4.1 to 25.8 hr) was greater than that observed in normal subjects of 2.2 hr (range: 1.6 to 2.4 hr) [see Dosage and Administration ( 2.2), Warnings and Precautions ( 5.8), Use in Specific Populations ( 8.7)].

Renal Impairment — The pharmacokinetics of zolpidem tartrate was studied in 11 patients with end-stage renal failure (mean Cl Cr = 6.5 ± 1.5 mL/min) undergoing hemodialysis three times a week, who were dosed with zolpidem tartrate 10 mg orally each day for 14 or 21 days. No statistically significant differences were observed for C max, T max, half-life, and AUC between the first and last day of drug administration when baseline concentration adjustments were made. Zolpidem was not hemodialyzable. No accumulation of unchanged drug appeared after 14 or 21 days. Zolpidem pharmacokinetics were not significantly different in renally impaired patients. No dosage adjustment is necessary in patients with compromised renal function.