Paroxetine-induced conversion of cytochrome P450 2D6 phenotype and occurence of adverse effects.
The paper is focused on a comparison of the distribution of side effects of treatment with paroxetine within a group of 30 patients genotyped and phenotyped for their CYP 2D6 metabolic status. Genotyping procedure showed that the patient group did not include any individual with poor metabolizer (PM) genotype; on the other hand, most patients (24) were classified as PMs by virtue of their phenotype, which suggests that a conversion to the poor metabolic phenotype ("phenocopy") occurred, probably as a consequence of a long-term administration of the strong CYP 2D6 inhibitor paroxetine. As to the occurence of common adverse effects, no marked difference between subjects converted into the PM group and those who had no history of such conversion was found. A significantly higher incidence of sexual dysfunction (p < 0.05) was, nevertheless, recorded in patients with the PM phenotype. The results of the study may provide evidence that it is the metabolic phenotype status, rather than the genetically given enzyme capacity (CYP 2D6 genotype), that is relevant for the actual toleration of treatment with CYP 2D6 inhibitors.
Zourková
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A
Department of Psychiatry, Masaryk University, Brno, Czech Republic. azourkova@fnbrno.cz
Hadasová
E
E
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000009:adverse effects; D019389:Cytochrome P-450 CYP2D6 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D003863:Depression / Q000145:classification / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000008:administration & dosage* / Q000009:adverse effects*; D010641:Phenotype; D020018:Sexual Dysfunctions, Psychological / Q000209:etiology; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D017374:Paroxetine; D019389:Cytochrome P-450 CYP2D6