Pharmacological Classification: Antidepressant.
Pharmacology: Pharmacodynamics: Mechanism of action: Escitalopram is a selective inhibitor of serotonin (5-HT)-uptake. Escitalopram has minimal eﬀect on noradrenaline (NA), dopamine (DA) and gamma aminobutyric acid (GABA) uptake. Escitalopram has no or very low aﬃnity for a series of receptors including 5-HT1A, 5-HT2, DA, D1 and D2 receptors, alpha1-, alpha2-, beta-adrenoceptors, histamine H1, muscarine cholinergic, benzodiazepine and opioid receptors.
Pharmacokinetics: Absorption: Absorption is independent of food intake (mean Tmax is 4 hours after multiple dosing).
Distribution: The apparent volume of distribution (Vd, a/F) after oral administration is about 12 to 26 L/kg. The plasma protein binding of escitalopram is approximately 55%.
Biotransformation: Escitalopram is metabolised in the liver to the demethylated and didemethylated Metabolite. Alternatively, the nitrogen may be oxidised to form the N-oxide metabolite. Both parent substance and metabolites are partly excreted as glucuronides. Unchanged Escitalopram is the predominant compound in plasma. After multiple dosing the mean concentrations of the demethyl- and didemethyl metabolites are usually 28 - 31% and <5% of the escitalopram concentration, respectively. Biotransformation of escitalopram to the demethylated metabolite is mediated by a combination of CYP2C19, CYP3A4 and CYP2D6.
Elimination: The elimination half-life (t½ beta) after multiple dosing is about 30 hours and the oral plasma clearance (ClOral) is about 0.6 L/min. Escitalopram and major metabolites are - like racemic citalopram - assumed to be eliminated both by the hepatic (metabolic) and the renal routes with the major part of the dose excreted as metabolites in urine. Hepatic clearance is mainly by the P450 enzyme system. CYP2C19 is the primary isoenzyme involved in the demethylation of Escitalopram, followed by CYP3A4 and CYP2D6.