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Drug Interactions

Metabolized principally by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6.

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction.

Specific Drugs

Pharmacokinetics

Absorption

Bioavailability

Conventional tablets: Rapidly absorbed following oral administration, with peak plasma concentrations attained in about 1.6 hours. Absolute bioavailability is about 70%.

Extended-release tablets: Exhibit biphasic absorption characteristics; rapid initial absorption following oral administration (similar to conventional tablets), but with extended plasma concentrations beyond 3 hours after administration. Peak plasma concentrations are attained in about 1.5 hours.

Food

Conventional tablets: Food decreases AUC by 15%, decreases peak plasma concentration by 25%, and prolongs time to peak plasma concentration by 60%.

Extended-release tablets: Food decreases AUC by 23%, decreases peak plasma concentration by 30%, and prolongs time to peak plasma concentration by about 2 hours (from 2 hours to 4 hours).

Special Populations

In geriatric patients receiving zolpidem tartrate as conventional tablets, peak plasma concentration and AUC are increased by 50 and 64%, respectively, compared with younger adults.

In patients with chronic hepatic impairment receiving zolpidem tartrate as conventional tablets, peak plasma concentration and AUC are 2 and 5 times higher, respectively, than in healthy individuals. Zolpidem tartrate extended-release tablets not studied to date in patients with hepatic impairment.

Distribution

Extent

Distributed into breast milk in small amounts. Not known whether zolpidem crosses the placenta.

Plasma Protein Binding

Approximately 92%.

Elimination

Metabolism

Metabolized in the liver via oxidation and hydroxylation, principally by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6. No active metabolites.

Elimination Route

Excreted principally in urine as inactive metabolites.

Half-life

Approximately 2.5 hours (conventional tablets) or 2.8 hours (extended-release tablets).

Special Populations

In geriatric patients receiving zolpidem tartrate as conventional tablets, half-life is increased by 32% compared with younger adults. Half-life is 2.9 hours in geriatric patients receiving zolpidem tartrate 6.25 mg as extended-release tablets.

In patients with cirrhosis receiving zolpidem tartrate as conventional tablets, half-life is about 9.9 hours. Extended-release tablets not studied to date in patients with hepatic impairment.

In nondialyzed patients with chronic renal disease and in patients undergoing periodic dialysis, slower elimination rates reported with IV zolpidem (not commercially available in the US). No substantial pharmacokinetic alterations reported with oral zolpidem in patients with end-stage renal failure undergoing hemodialysis. Extended-release tablets not studied to date in patients with renal impairment.

Not removed by hemodialysis.

Stability

Storage

Oral

Conventional Tablets

20–25°C.

Extended-release Tablets

15–25°C (may be exposed to temperatures up to 30°C).

Actions

• Interacts with the CNS GABA_A-receptor-chloride ionophore complex at benzodiazepine (BZ, ο) receptors.
• Selectivity for the BZ₁ receptor may account for the decreased muscle relaxant, anxiolytic, and anticonvulsant effects compared with benzodiazepines reported in animal studies, as well as the preservation of deep sleep (stages 3 and 4) reported in human studies.