Comparative pharmacokinetics of selective serotonin reuptake inhibitors: a look behind the mirror
Details
Serval ID
serval:BIB_05A4ED147BB7
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Comparative pharmacokinetics of selective serotonin reuptake inhibitors: a look behind the mirror
Journal
International Clinical Psychopharmacology
ISSN
0268-1315 (Print)
Publication state
Published
Issued date
03/1995
Volume
10 Suppl 1
Pages
15-21
Notes
Journal Article
Research Support, Non-U.S. Gov't
Review --- Old month value: Mar
Research Support, Non-U.S. Gov't
Review --- Old month value: Mar
Abstract
The presently available selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, despite their common mechanism of action, differ in their chemical structure, metabolism and pharmacokinetics. From a clinical point of view, it is of relevance that potency to inhibit the cytochrome P450 isozyme CYP2D6 gradually decreases from paroxetine, fluoxetine, norfluoxetine, desmethylcitalopram, fluvoxamine, and sertraline down to citalopram, explaining to a great extent differences in pharmacokinetic interactions between the SSRIs and tricyclic antidepressants, which are metabolized by this enzyme. Fluvoxamine interacts with these drugs by a mechanism involving inhibition of CYP1A2, CYP3A4, and CYP2C19. Except for paroxetine, a substrate of CYP2D6, little is known about the enzymes implicated in the metabolism of SSRIs. Fluoxetine and citalopram are used as racemic drugs. Data on the stereoselectivity of their enantiomers in the inhibition of serotonin (5-HT) uptake in the animal brain, also those available on their metabolism and kinetics in humans, are presented. It may be concluded that for routine therapeutic drug monitoring, the plasma level measurement of the enantiomers of citalopram and fluoxetine is probably of little relevance. However, for the study of the structure-activity relationship between these drugs and the cerebral 5-HT transporter, the stereochemical differences of these enantiomers should be considered. In this sense, the enantiomers of these drugs could represent a promising tool to increase present knowledge.
Keywords
1-Naphthylamine/analogs & derivatives/pharmacokinetics
Animals
Citalopram/pharmacokinetics
Cytochrome P-450 Enzyme System/metabolism
Depressive Disorder/drug therapy
Fluoxetine/pharmacokinetics
Fluvoxamine/pharmacokinetics
Humans
Paroxetine/pharmacokinetics
Serotonin Uptake Inhibitors/*pharmacokinetics/therapeutic use
Sertraline
Stereoisomerism
Pubmed
Web of science
Create date
25/01/2008 9:47
Last modification date
20/08/2019 13:27