Text Version
Entrez PubMed
Overview
Help | FAQ
Tutorial
New/Noteworthy
E-Utilities
PubMed Services
Journals Database
MeSH Database
Single Citation Matcher
Batch Citation Matcher
Clinical Queries
LinkOut
Cubby
Related Resources
Order Documents
NLM
Gateway
TOXNET
Consumer
Health
Clinical Alerts
ClinicalTrials.gov
PubMed
Central
Privacy Policy
|
 |
-
Differences in interactions of
SSRIs.
Brosen K.
Department of Clinical
Pharmacology, Institute of Medical Biology, Odense University,
Denmark.
The SSRIs differ from each other with regard to their
chemical structure, their pharmacokinetics and their potential for
causing pharmacokinetic interactions through inhibition of species of
the cytochrome P450 enzyme system. Cytochrome P450 (CYP) is a group of
more than 30 different heme containing proteins in humans, some of which
play a key role in the oxidation and hence the elimination of numerous
drugs, including the SSRIs. Thus fluvoxamine, but not citalopram,
fluoxetine, paroxetine and sertraline is a potent inhbitor of CYP1A2.
Accordingly fluvoxamine has interactions with other drugs eliminated by
CYP1A2 including caffeine, clozapine, olanzapine, theophylline,
propranolol and tacrine. CYP2C19 is the source of the S-mephenytoin
oxidation polymorphism. About 2% of whites are poor metabolizers in whom
CYP2C19 is not expressed. Poor metabolizers have an impaired elimination
of among other drugs citalopram. Although not metabolized by CYP2C19,
fluvoxamine is still a potent inhibitor of the enzyme. The same applies
to fluoxetine. CYP2D6 only makes up about 2-5% of the total P450 in the
human liver, but anyway is the major enzyme catalyzing more than 30
clinically used drugs including all of the tricyclic antidepressants,
several neuroleptics, opiates, betablockers, antiarrhythmics and among
the SSRIs N-desmethylcitalopram, fluvoxamine, fluoxetine and paroxetine
but not sertraline. All of the SSRIs inhibit CYP2D6 but fluoxetine,
norfluoxetine and paroxetine are particularly potent inhibitors. CYP3A4
is the most abundant human cytochrome P450, but most of the SSRIs with
the exception of norfluoxetine do not inhibit this enzyme, and
interactions with SSRIs and CYP3A4 appear not to be a
significant.
Publication Types:
PMID: 9817620 [PubMed - indexed for
MEDLINE]
|