| Item |
Information |
|
Drug Groups
|
illicit; approved |
|
Description
|
A benzodiazepine with anticonvulsant, hypnotic, and muscle relaxant properties. It has been shown in some cases to be more potent than diazepam or nitrazepam. [PubChem] |
| Indication |
For the short-term management of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. |
| Pharmacology |
Estazolam, a triazolobenzodiazepine derivative, is an oral hypnotic agent with anticonvulsant, hypnotic, and muscle relaxant properties. It has been shown in some cases to be more potent than diazepam or nitrazepam. |
| Toxicity |
Symptoms of overdose include confusion, depressed breathing, drowsiness and eventually coma, lack of coordination, and slurred speech. |
| Affected Organisms |
| • |
Humans and other mammals |
|
| Biotransformation |
Extensively metabolized in the liver. In vitro studies with human liver microsomes indicate that the biotransformation of estazolam to the major circulating metabolite 4-hydroxy-estazolam is mediated by cytochrome P450 3A (CYP3A). |
| Absorption |
Tablets have been found to be equivalent in absorption to an orally administered solution of estazolam. In healthy subjects who received up to three times the recommended dose, peak estazolam plasma concentrations occurred within two hours after dosing (range 0.5 to 6.0 hours) and were proportional to the administered dose, suggesting linear pharmacokinetics over the dosage range tested. |
| Half Life |
The range of estimates for the mean elimination half-life of estazolam varies from 10 to 24 hours. |
| Protein Binding |
93% protein bound, independant of concentration. |
| Elimination |
Estazolam is extensively metabolized. The elimination of the parent drug takes place via hepatic metabolism of estazolam to hydroxylated and other metabolites that are eliminated largely in the urine both free and conjugated. Less than 5% of a 2 mg dose of estazolam was excreted unchanged in the urine, with only 4% of the dose appearing in the feces. Radiolabel mass balance studies indicate that the main route of excretion is via the kidneys. After 5 days, 87% of the administered radioactivity was excreted in human urine. Less than 4% of the dose was excreted unchanged. |
| References |
| • |
Watanabe S, Ohta H, Sakurai Y, Takao K, Ueki S: [Electroencephalographic effects of 450191-S and its metabolites in rabbits with chronic electrode implants] Nippon Yakurigaku Zasshi. 1986 Jul;88(1):19-32.
[Pubmed]
|
| • |
Oishi R, Nishibori M, Itoh Y, Saeki K: Diazepam-induced decrease in histamine turnover in mouse brain. Eur J Pharmacol. 1986 May 27;124(3):337-42.
[Pubmed]
|
| • |
Usami N, Yamamoto T, Shintani S, Ishikura S, Higaki Y, Katagiri Y, Hara A: Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines. Biol Pharm Bull. 2002 Apr;25(4):441-5.
[Pubmed]
|
|
| External Links |
|