Relationship between fluvoxamine pharmacokinetics and CYP2D6/CYP2C19 phenotype polymorphisms

The purpose of this study was to investigate whether the disposition of fluvoxamine is associated with the CYP2D6 and CYP2C19 phenotype polymorphisms. The serum concentration of fluvoxamine was followed for 48 h after oral administration of a single dose of 50 mg fluvoxamine to five poor metabolizer...

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Bibliographic Details
Published in:European journal of clinical pharmacology 1997, Vol.52 (2), p.129-133
Main Authors: SPIGSET, O, GRANBERG, K, HÄGG, S, NORSTRÖM, A, DAHLQVIST, R
Format: Article
Language:English
Subjects:
Adult
Antidepressive Agents, Second-Generation - adverse effects
Antidepressive Agents, Second-Generation - pharmacokinetics
Aryl Hydrocarbon Hydroxylases
Biological and medical sciences
Cytochrome P-450 CYP2C19
Cytochrome P-450 CYP2D6 - genetics
Cytochrome P-450 CYP2D6 - metabolism
Cytochrome P-450 Enzyme System - genetics
Cytochrome P-450 Enzyme System - metabolism
Dextromethorphan - metabolism
Female
Fluvoxamine - adverse effects
Fluvoxamine - pharmacokinetics
Genotype & phenotype
Humans
Male
Medical sciences
Medical treatment
Mixed Function Oxygenases - genetics
Mixed Function Oxygenases - metabolism
Neuropharmacology
Pharmacology. Drug treatments
Phenotype
Polymorphism, Genetic
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
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Summary:The purpose of this study was to investigate whether the disposition of fluvoxamine is associated with the CYP2D6 and CYP2C19 phenotype polymorphisms. The serum concentration of fluvoxamine was followed for 48 h after oral administration of a single dose of 50 mg fluvoxamine to five poor metabolizers of the CYP2D6 test drug dextromethorphan, five poor metabolizers of the CYP2C19 test drug mephenytoin, and five extensive metabolizers of both test drugs. Poor metabolizers of dextromethorphan had significantly higher areas under the serum concentration-time curve than extensive metabolizers of dextromethorphan (mean 1.31 vs 1.00 mumol.h.l-1). There were no differences between poor and extensive metabolizers of mephenytoin (mean, 1.00 vs 1.15 mumol.h.l-1). The results are consistent with a possible minor to moderate role of CYP2D6, but not CYP2C19, in fluvoxamine metabolism.
ISSN:0031-6970
1432-1041
DOI:10.1007/s002280050261