The clinical pharmacokinetics of escitalopram.
Article Details
- CitationCopy to clipboard
Rao N
The clinical pharmacokinetics of escitalopram.
Clin Pharmacokinet. 2007;46(4):281-90. doi: 10.2165/00003088-200746040-00002.
- PubMed ID
- 17375980 [ View in PubMed]
- Abstract
Escitalopram is the (S)-enantiomer of the racemic selective serotonin reuptake inhibitor antidepressant citalopram. Clinical studies have shown that escitalopram is effective and well tolerated in the treatment of depression and anxiety disorders. Following oral administration, escitalopram is rapidly absorbed and reaches maximum plasma concentrations in approximately 3-4 hours after either single- or multiple-dose administration. The absorption of escitalopram is not affected by food. The elimination half-life of escitalopram is about 27-33 hours and is consistent with once-daily administration. Steady-state concentrations are achieved within 7-10 days of administration. Escitalopram has low protein binding (56%) and is not likely to cause interactions with highly protein-bound drugs. It is widely distributed throughout tissues, with an apparent volume of distribution during the terminal phase after oral administration (V(z)/F) of about 1100L. Unmetabolised escitalopram is the major compound in plasma. S-demethylcitalopram (S-DCT), the principal metabolite, is present at approximately one-third the level of escitalopram; however, S-DCT is a weak inhibitor of serotonin reuptake and does not contribute appreciably to the therapeutic activity of escitalopram. The didemethyl metabolite of escitalopram (S-DDCT) is typically present at or below quantifiable concentrations. Escitalopram and S-DCT exhibit linear and dose-proportional pharmacokinetics following single or multiple doses in the 10-30 mg/day dose range. Adolescents, elderly individuals and patients with hepatic impairment do not have clinically relevant differences in pharmacokinetics compared with healthy young adults, implying that adjustment of the dosage is not necessary in these patient groups. Escitalopram is metabolised by the cytochrome P450 (CYP) isoenzymes CYP2C19, CYP2D6 and CYP3A4. However, ritonavir, a potent inhibitor of CYP3A4, does not affect the pharmacokinetics of escitalopram. Coadministration of escitalopram 20mg following steady-state administration of cimetidine or omeprazole led to a 72% and 51% increase, respectively, in escitalopram exposure compared with administration alone. These changes were not considered clinically relevant. In vitro studies have shown that escitalopram has negligible inhibitory effects on CYP isoenzymes and P-glycoprotein, suggesting that escitalopram is unlikely to cause clinically significant drug-drug interactions. The favourable pharmacokinetic profile of escitalopram suggests clinical utility in a broad range of patients.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Escitalopram Aldehyde oxidase Protein Humans NoSubstrateDetails Escitalopram Amine oxidase [flavin-containing] A Protein Humans NoSubstrateDetails Escitalopram Amine oxidase [flavin-containing] B Protein Humans NoSubstrateDetails Escitalopram Cytochrome P450 2D6 Protein Humans NoSubstrateInhibitorDetails Escitalopram Cytochrome P450 3A4 Protein Humans NoSubstrateDetails - Drug Reactions
Reaction Details Details - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareEscitalopramBoceprevir The serum concentration of Escitalopram can be decreased when it is combined with Boceprevir.
