Fluvoxamine is a potent inhibitor of the metabolism of caffeine in vitro.
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Rasmussen BB, Nielsen TL, Brosen K
Fluvoxamine is a potent inhibitor of the metabolism of caffeine in vitro.
Pharmacol Toxicol. 1998 Dec;83(6):240-5.
- PubMed ID
- 9868741 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Fluvoxamine Cytochrome P450 1A2 Protein Humans UnknownSubstrateInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAminophyllineFluvoxamine The metabolism of Aminophylline can be decreased when combined with Fluvoxamine. BromotheophyllineFluvoxamine The metabolism of Bromotheophylline can be decreased when combined with Fluvoxamine. CaffeineFluvoxamine The metabolism of Caffeine can be decreased when combined with Fluvoxamine. ClozapineFluvoxamine The serum concentration of Clozapine can be increased when it is combined with Fluvoxamine. DyphyllineFluvoxamine The metabolism of Dyphylline can be decreased when combined with Fluvoxamine.