Source: Health Products Regulatory Authority (ZA) Revision Year: 2019 Publisher: CIPLA MEDPRO (PTY) LTD., Building 9, Parc du Cap, Mispel Street, Bellville, 7530
A 1.2 Psychoanaleptics (antidepressants)
Escitalopram selectively inhibits the uptake of serotonin (5-HT). Escitalopram has minimal effect on the uptake of the following neurotransmitters: noradrenaline (NA), dopamine (DA) and gamma aminobutyric acid (GABA). Escitalopram also shows no or very low affinity for the following receptors: 5-HT1A, 5-HT2, DA (D1- and D2- receptors), α1, α2, β-adrenoceptors, histamine H1, muscarinic receptors, benzodiazepine, and opioid receptors.
Escitalopram has a modulating effect on the transporter of serotonin and a high affinity for the primary binding site. A more complete serotonin reuptake inhibition is a result of allosteric modulation of the serotonin transporter enhancing the binding of escitalopram to the primary binding site.
Absorption is not influenced by food intake (mean Tmax is 4 hours after multiple dosing).
The apparent volume of distribution after oral administration ranges from approximately 12 to 26 L/kg. Escitalopram has a plasma protein binding of approximately 55%.
The liver metabolises escitalopram to the demethylated and didemethylated metabolites. Alternatively, through oxidation, the nitrogen may be converted to the N-oxide metabolite. The parent substance as well as metabolites are partly excreted as glucuronides.
In plasma escitalopram occurs predominantly as the unchanged compound. After multiple dosing the mean concentration of the demethyl metabolites ranges from 28% to 31%, while that of the didemethyl metabolites is less than 5% of the escitalopram concentration. A combination of CYP2C19, CYP3A4 and CYP2D6 is responsible for the biotransformation of escitalopram to the demethylated metabolite.
Escitalopram has an elimination half-life after multiple dosing of approximately 30 hours. The plasma clearance after oral administration (Cloral) is approximately 0,6 L/min. It is assumed that, similar to racemic citalopram, escitalopram and its major metabolites are eliminated both by the hepatic (metabolic) and renal routes, but that renal excretion of the metabolites is the principal route of elimination.
The P450 enzyme system is mainly responsible for hepatic clearance with CYP2C19, the primary isoenzyme involved in the demethylation of escitalopram, followed by CYP3A4 and CYP2D6. Escitalopram exhibits linear pharmacokinetics. It takes approximately 1 week to reach steady state plasma levels. With a daily dose of 10 mg steady state concentrations average 50 nmol/L (range 20 to 125 nmol/L).
The half-life of escitalopram is increased in the elderly (approximately 50%), while decreased clearance values, due to a reduced rate of metabolism, have also been demonstrated in this patient group.
Although escitalopram is eliminated more slowly in patients with mild to moderate impairment of renal function, mild to moderate renal impairment does not have a major impact on the serum concentration of escitalopram. At present no information is available for the treatment of patients who suffer from severely reduced renal function (creatinine clearance less than 30 mL/min).
In patients with reduced hepatic function the half-life of escitalopram is double that seen in patients with normal liver function. Steady state escitalopram concentrations at a given dose will be approximately twice as high compared to patients with normal hepatic function.
Based on the results of in vitro trials with escitalopram and in vivo trials with racemic citalopram, genetic polymorphism with respect to CYP2D6 is not known, while it may be of clinical relevance with respect to CYP2C19.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.