Linked Life Data

9868741

Source:http://linkedlifedata.com/resource/pubmed/id/9868741

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1999-3-15
pubmed:abstractText
The selective serotonin re-uptake inhibitor, fluvoxamine, is a very potent inhibitor of CYP1A2, and accordingly causes pharmacokinetic interactions with drugs metabolised by CYP1A2, such as caffeine, theophylline, imipramine, tacrine and clozapine. Interaction between caffeine and fluvoxamine has been described in vivo, leading to lowering of total clearance of caffeine by 80% during fluvoxamine intake. The main purpose of the present study was to evaluate this interaction in vitro in human liver microsomes. A high-performance liquid chromatography method was developed in order to assay 1,3-dimethylxanthine, 1,7-dimethylxanthine, 3,7-dimethylxanthine and 1,3,7-trimethyluric acid formed from caffeine by human liver microsomes. The limit of detection was 0.06 nmol.mg protein-1.hr-1. As expected, fluvoxamine was a very potent inhibitor of the formation of the N-demethylated caffeine metabolites, displaying Ki values of 0.08-0.28 microM. The formation of 1,7-dimethylxanthine was virtually abolished by 10 microM of fluvoxamine, indicating that the N3-demethylation of caffeine is almost exclusively catalysed by CYP1A2. The CYP3A4 inhibitors, ketoconazole and bromocriptine, inhibited 1,3,7-trimethyluric acid formation with Kis of 0.75 microM and 5 microM, respectively, thus further supporting the involvement of CYP3A4 in the 8-hydroxylation of caffeine. The study shows that fluvoxamine, as expected, is a potent inhibitor of the metabolism of caffeine in vitro.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0901-9928
pubmed:author
pubmed:issnType
Print
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
240-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Fluvoxamine is a potent inhibitor of the metabolism of caffeine in vitro.
pubmed:affiliation
Department of Clinical Pharmacology, Odense University, Denmark.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't