Jovia

Jovia Mechanism of Action

escitalopram

Manufacturer:

Medichem

Distributor:

United Lab
Full Prescribing Info
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Pharmacology: Escitalopram, the active S-enantiomer of racemic citalopram, is a highly potent and selective inhibitor of the serotonin transporter protein which is responsible for serotonin (5-HT) reuptake into presynaptic nerve terminals in the central nervous system (CNS).
Escitalopram has a primary high-affinity binding site and a secondary lower-affinity allosteric site in the serotonin transporter protein. Binding of escitalopram to the allosteric site enhances binding of the drug to the primary binding site, resulting in more complete serotonin reuptake inhibition. This also explains the enhanced potency of escitalopram compared with citalopram.
In vitro studies showed that escitalopram had no, or minimal effect on noradrenaline (NA), dopamine (DA) and gamma-amino butyric acid (GABA) uptake.
Compared with many tricyclic antidepressants (TCAs) and some of the selective serotonin reuptake inhibitors (SSRIs), escitalopram has no or very low affinity for a number of receptors such as 5-HT1A, 5-HT2, DA D1 and DA D2 receptors, α1-, α2-, β-adrenoceptors, histamine H1, muscarine cholinergic, benzodiazepine and opioid receptors.
Pharmacokinetics: Escitalopram's absorption is almost complete and independent of food intake. As with racemic citalopram, the absolute bioavailability of escitalopram is about 80%.
After multiple dosing, mean time to maximum concentration (mean Tmax) is about four hours. Escitalopram exhibits linear pharmacokinetics. Steady-state plasma levels are achieved in about one week.
Escitalopram is widely distributed throughout tissues, with an apparent volume of distribution after oral administration of 1,100 L. It exhibits low protein-binding (average 56%) over a wide range of concentrations, indicating a low potential for drug displacement interactions.
Escitalopram is metabolized in the liver to less lipophilic compounds that are readily excreted in urine. Biotransformation of the drug occurs via oxidative metabolism with N-demethylation to S-demethylcitalopram (S-DCT) and S-didemethylcitalopram (S-DDCT), deamination and dehydrogenation to a propionic acid derivative, and also N-oxidation and glucuronide conjugation. N-demethylation of escitalopram to S-DCT is mediated by three hepatic CYP isoenzymes in parallel, CYP3A4, CYP2C19 and, to a lesser extent, CYP2D6. After multiple dose administration of citalopram, poor metabolizers of CYP2C19 had higher plasma concentrations of escitalopram and lower concentrations of S-DCT than extensive metabolizers; however, the urinary recovery and renal clearance of escitalopram and its metabolites did not differ significantly between the two phenotypes. The metabolites of escitalopram are unlikely to contribute to the clinical effects, since they are present at much lower concentrations in vivo and have been shown in vitro to be much weaker inhibitors of serotonin reuptake.
Escitalopram's elimination half-life (t½) is about 30 hrs. Oral plasma clearance is 0.6 L/min. Escitalopram and its metabolites are eliminated by both hepatic and renal routes, with major part of the dose excreted as metabolites in the urine.
Special Population: Hepatic Impairment: In patients with mild to moderate hepatic impairment (Child-Pugh Criteria A and B), the t½ of escitalopram was about twice as long and the exposure was about 60% higher than in subjects with normal liver function. The dose of escitalopram should therefore be reduced in such patients.
Renal Impairment: The pharmacokinetics of escitalopram in patients with renal impairment have not been explicitly investigated. However, in patients with mild to moderate renal impairment (creatinine clearance 10 to 53 mL/min), the t½ of a single dose of citalopram was increased by approximately 35%, with oral and renal clearance being about 15% and 40% lower, respectively, than in healthy volunteers. Plasma concentrations of the metabolites have not been studied, but it may be elevated.
Geriatrics: Escitalopram AUC and half-life were increased by approximately 50% in the elderly (>65 years); Cmax was unchanged. A lower initial dosage should be considered.
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