DOI: 10.1097/01.jcp.0000203225.79364.85
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PMID: 16633156
Issn Print: 0271-0749
Publication Date: 2006/04/01
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Excerpt
Although no clear-cut concentration-effect relationship has been revealed for the selective serotonin reuptake inhibitor, paroxetine, serum concentration measurements are frequently used to optimize treatment results.1-3 Like many other antidepressants, paroxetine is metabolized by the hepatic isoenzyme cytochrome P 450 (CYP) 2D6.4 CYP2D6 is a polymorphic enzyme that exerts a considerable genetically determined interindividual variability in metabolic capacity.
In 2 recent studies, the influence of CYP2D6 genotype on paroxetine plasma concentrations has been investigated in clinical settings.5,6 In one of these,5 the occurrence of the partially or completely inactivating mutations CYP2D6*5 and CYP2D6*10 was associated with higher paroxetine concentrations in a Japanese population. No ultrarapid metabolizers were revealed in that study. In the other study,6 conducted in Belgium, the mean plasma concentration of paroxetine was more than 3-fold higher in genotypically CYP2D6 poor metabolizers than in extensive metabolizers. Only one ultrarapid metabolizer was identified, which can readily be explained by the small sample size (n = 37), as the frequency of genotypically ultrarapid metabolizers in Northern European populations is a few percent only.7 In this ultrarapid metabolizer,6 the plasma concentration of paroxetine was found to be below the limit of detection (which was not specifically stated) during treatment with a dose of 20 mg/d.
As we have not identified other reports addressing the impact of the CYP2D6 ultrarapid metabolizer genotype on the paroxetine plasma levels, we describe 2 patients with very low serum concentrations of paroxetine who were subsequently genotyped and found to be CYP2D6 ultrarapid metabolizers. Moreover, we compare their paroxetine levels to the serum concentrations found in more than 1400 samples obtained from our routine therapeutic drug-monitoring database.
