The effect of perazine on the CYP2D6 and CYP2C19 phenotypes as measured by the dextromethorphan and mephenytoin tests in psychiatric patients.

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State: Public
Version: Author's accepted manuscript
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Serval ID
serval:BIB_D5D86F76E23B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The effect of perazine on the CYP2D6 and CYP2C19 phenotypes as measured by the dextromethorphan and mephenytoin tests in psychiatric patients.
Journal
Basic & clinical pharmacology & toxicology
Author(s)
Baumann P., Eap C.B., Gastpar M.
ISSN
1742-7843 (Electronic)
ISSN-L
1742-7835
Publication state
Published
Issued date
05/2020
Peer-reviewed
Oui
Volume
126
Number
5
Pages
444-447
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
There is evidence that the antipsychotic drug perazine is an inhibitor of CYP2D6. This study aimed at evaluating its effect on CYP2D6 and CYP2C19 activities in submitting psychiatric patients to phenotyping with dextromethorphan and mephenytoin, respectively, substrates of these enzymes, before and during a treatment with perazine. A total of 31 patients were phenotyped with dextromethorphan (CYP2D6) and mephenytoin (CYP2C19) before and after a 2-week treatment with 450 ± 51 mg/day (mean ± sd) perazine. At baseline, five patients appeared to be poor metabolizers (PM) of dextromethorphan and two patients of mephenytoin. The metabolic ratio (MR) of dextromethorphan/dextrorphan as determined in collected urine increased significantly (Wilcoxon; P < .0001) from baseline (0.39 ± 1.38 [mean ± sd]) till day 14 (1.46 ± 2.22). In 19 out of 26 extensive metabolizers (EM) of dextromethorphan, the phenotype changed from EM to PM. This suggests an almost complete inhibition of CYP2D6 by perazine and/or its metabolites. On the other hand, perazine (or some of its metabolites) did seemingly not inhibit CYP2C19. In conclusion, this study suggests that in patients treated with perazine and co-medicated with CYP2D6 substrates, there could be an increased risk of adverse effects as a consequence of a pharmacokinetic interaction.
Keywords
CYP2C19, CYP2D6, Perazine, pharmacogenetics, pharmacokinetic interaction, psychiatric patients, Pharmacogenetics, perazine
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Web of science
Create date
15/12/2019 18:22
Last modification date
06/05/2020 6:20
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