Золпидем тартрат

Химические свойства

White or almost white, hygroscopic, crystalline powder.

Использование

Sedativehypnotic.

Определение

ChEBI: The hemitartrate salt of zolpidem.

Фармакокине?тика

Zolpidem exhibits a high selectivity for the α1 subunit. Its good bioavailability of 72% and rapid onset of action of approximately 1.4 hours following oral absorption can be attributed to its weak base (pKa = 6.2) and high lipophilicity (mlog P = 3.85). Its pharmacokinetic profile is characterized by rapid absorption from the gastrointestinal tract and a short elimination half-life because of rapid oxidative metabolism to inactive carboxylic acid metabolites. Zolpidem undergoes CYP3A4 (major), CYP2DG, and CYP2D6 hydroxylation of the aryl methyl groups, followed by further oxidation by aldehyde dehydrogenase to the ionic carboxylic acids, which are readily eliminated in the urine.
Zolpidem demonstrates linear (dose-proportional) kinetics in the dose range of 5 to 20 mg. Although protein binding was 90%, no drug accumulation was observed following nightly dosing with 20-mg zolpidem tartrate tablets for 2 weeks. Food can prolong the time to peak concentration from 1.4 to 2.2 hours without affecting the half-life. These results suggest that for faster sleep onset, zolpidem should not be administered with or immediately after a meal. In the elderly, the dose should be 5 mg, because the elimination half-life is increased by 50% (from ~2 to ~3 hours). No accumulation was observed in elderly subjects following nightly oral dosing of 10 mg for 1 week. In patients with hepatic insufficiency, the plasma concentration doubled with an increase in the elimination half-life from approximately 2 to approximately 10 hours (range, 4–25 hours). Therefore, dosing should be modified in patients with hepatic insufficiency. No dosage adjustment should be necessary in patients with compromised renal function. Zolpidem is not hemodialyzable, but it does cross the placenta and into breast milk. Because of its longer elimination half-life (when compared to zaleplon), it may be preferred when sleep maintenance is a primary concern.