Pharmacology: Pharmacodynamics: Escitalopram Oxalate is an orally administered selective serotonin reuptake inhibitor (SSRI). Escitalopram is the pure S-enantiomer (single isomer) of the racemic bicyclic phthalane derivative citalopram. The mechanism of antidepressant action of Escitalopram, the S-enantiomer of racemic citalopram, is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT). Escitalopram is at least 100 fold more potent than the R-enantiomer with respect to inhibition of 5-HT reuptake and inhibition of 5-HT neuronal firing rate.
Escitalopram has no or very low affinity for serotonergic (5-HT1-7) or other receptors including alpha- and beta-adrenergic, dopamine (D1-5), histamine (H1-3), muscarinic (M1-5) and benzodiazepine receptors. Escitalopram also does not bind to or has low affinity for various ion channels including Na+, K+, Cl- and Ca++ channels. Antagonism of muscarinic, histaminergic and adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative and cardiovascular side effects of other psychotropic drugs.
Pharmacokinetics: The single and multiple dose pharmacokinetics of Escitalopram are linear and dose-proportional in a dose range of 10 to 30 mg/day. Biotransformation of Escitalopram is mainly hepatic, with a mean terminal hall-life of about 27-32 hours. With once daily dosing, steady state plasma concentrations are achieved within approximately one week. At steady state, the extent of accumulation of Escitalopram in plasma in young healthy subjects was 2.2-2.5 times the plasma concentrations observed after a single dose.
Absorption and Distribution: Following a single oral dose (20 mg tablet) of Escitalopram, the mean Tmax was 5 ± 1.5 hours.
Absorption of Escitalopram is not affected by food.
The absolute bioavailability of citalopram is about 80% relative to an intravenous dose, and the volume of distribution of citalopram is about 12L/kg. Data specific to Escitalopram are unavailable. The binding of Escitalopram to human plasma proteins is approximately 56%.
Metabolism and Elimination: Following oral administrations of Escitalopram, the fraction of drug recovered in the urine as Escitalopram and S-demethycitalopram (S-DCT) is about 8% and 10% respectively. The oral clearance of the Escitalopram is 600 ml/min, with approximately 7% of that due to renal clearance.
Escitalopram is metabolized to S-DCT and S-didemethylcitalopram (S-DDCT). In humans, unchanged Escitalopram is the predominant compound in plasma. At steady state, the concentration of Escitalopram metabolite S-DCT in plasma is approximately one-third that of Escitalopram. CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of Escitalopram.