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Clinical Pharmacology
CLINICAL PHARMACOLOGY
Pharmacodynamics: Subunit modulation of the GABAA receptor chloride channel macromolecular complex is hypothesized to be responsible for sedative, anticonvulsant, anxiolytic, and myorelaxant drug properties. The major modulatory site of the GABAA receptor complex is located on its alpha () subunit and is referred to as the benzodiazepine (BZ) or omega () receptor. At least three subtypes of the () receptor have been identified. Text Continues Below
While zolpidem is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with a GABA-BZ receptor complex and shares some of the pharmacological properties of the benzodiazepines. In contrast to the benzodiazepines, which nonselectively bind to and activate all omega receptor subtypes, zolpidem in vitro binds the (1) receptor preferentially with a high affinity ratio of the alpha1/alpha5 subunits. The (1) receptor is found primarily on the Lamina IV of the sensorimotor cortical regions, substantia nigra (pars reticulata), cerebellum molecular layer, olfactory bulb, ventral thalamic complex, pons, inferior colliculus, and globus pallidus. This selective binding of zolpidem on the (1) receptor is not absolute, but it may explain the relative absence of myorelaxant and anticonvulsant effects in animal studies as well as the preservation of deep sleep (stages 3 and 4) in human studies of zolpidem at hypnotic doses. Pharmacokinetics: The pharmacokinetic profile of Ambien is characterized by rapid absorption from the GI tract and a short elimination half-life (T1/2) 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 (Cmax) were 59 (range: 29 to 113) and 121 (range: 58 to 272) ng/mL, respectively, occurring at a mean time (Tmax) of 1.6 hours for both. The mean Ambien 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. Page: 1 | 2 | 3 | 4 | 5 | Next >>
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