Source: Health Products Regulatory Authority (ZA) Revision Year: 2022 Publisher: RANBAXY PHARMACEUTICALS (PTY) LTD, 14 Lautre Road, Stormill, Ext.1, Roodepoort, 1724, South Africa
Category and class: A 2.6 Tranquilisers
Pharmacotherapeutic group: ATC code: N05BA01
Diazepam is a long-acting benzodiazepine hypnotic with anxiolytic, sedative, muscle-relaxant, anticonvulsant and amnesic properties.
The major sites of action of diazepam on the spinal reflexes are supraspinal. However, this action is in part mediated by the brain stem reticular system. It depresses the duration of electrical after discharge in the limbic system, including the septal region, amygdala and hippocampus. These actions result from potentiation of the neural inhibition that is mediated by Gamma-aminobutyric acid (GABA).
Diazepam is rapidly and completely absorbed from the gastrointestinal tract, peak plasma concentrations appearing 30 to 90 minutes after oral ingestion.
Diazepam and its metabolites are highly bound to plasma proteins (diazepam 98%). Diazepam and its metabolites cross the blood-brain and placental barriers and are also found in breast milk. The volume of distribution at steady state is 0,8-1,0 â„“/kg. The half-life of distribution is up to 3 hours.
Diazepam is mainly metabolised to the pharmacologically active metabolites such as Ndesmethyldiazepam, temazepam and oxazepam. The oxidative metabolism of diazepam is mediated by CYP3A and CYP2C19 isoenzymes. Oxazepam and temazepam are further conjugated to glucuronic acid.
The decline in the plasma concentration-time profiles after oral and i.v. administration of diazepam is biphasic; an initial rapid and extensive distribution phase being followed by a prolonged terminal elimination phase (half-life up to about 48 hours). The terminal elimination half-life of the active metabolite N-desmethyldiazepam is up to 100 hours. Diazepam and its metabolites are excreted mainly into the urine, predominantly in their conjugated forms. The clearance of diazepam is 20-30 mâ„“/min.
The elimination half-life may be prolonged in the newborn, in the elderly and in patients with liver disease. In renal impairment the half-life of diazepam is unchanged.
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