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Pharmacology: Diazepam is a long-acting benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant and amnestic properties. Its actions are mediated by enhancement of the activity of gamma-aminobutyric acid (GABA).
Pharmacokinetics: Absorption may be erratic following intramuscular administration of Diazepam and lower peak plasma concentrations may be obtained compared with those following oral administration. Diazepam is highly lipid soluble and crosses the blood-brain barrier, it acts promptly on the brain, and its initial effects decrease rapidly as it is redistributed into fat depots and tissues.
Diazepam has a biphasic half-life with an initial rapid distribution phase followed by a prolonged terminal elimination phase of 1 or 2 days; its action is further prolonged by the even longer half-life of 2 to 5 days of its principal active metabolite, desmethyldiazepam. Diazepam and desmethyldiazepam accumulate on repeated administration and the relative proportion of desmethyldiazepam in the body increases on long-term administration. No simple correlation has been found between plasma concentrations of diazepam or its metabolites and their therapeutic effect.
Diazepam is extensively metabolized in the liver. It is excreted in the urine, mainly in the form of free or conjugated metabolites.
Diazepam is 98 to 99% bound to plasma proteins.
The plasma elimination half-life of diazepam and/or its metabolites is prolonged in neonates, in the elderly, and in patients with liver disease. In addition to crossing the blood-brain barrier, diazepam and its metabolites also cross the placental barrier and are distributed into breast milk.
