Abstract
CYP2C19 converts the tricyclic antidepressant imipramine to its active metabolite desipramine, which is subsequently inactivated by CYP2D6. The novel CYP2C19*17 allele causes ultrarapid metabolism of CYP2C19 substrates. We genotyped 178 depressed patients on imipramine for CYP2C19*17, and measured steady-state imipramine and desipramine plasma concentrations. Mean dose-corrected imipramine plasma concentration was significantly dependent on CYP2C19 genotype (Kruskal–Wallis test, P=0.01), with circa 30% lower levels in CYP2C19*17/*17 individuals compared with CYP2C19*1/*1 (wild-type) patients. The mean dose-corrected imipramine+desipramine plasma concentrations and imipramine/desipramine ratios were not significantly different between genotype subgroups (Kruskal–Wallis tests, P⩾0.12). In a multivariate analysis, we found a significant, but limited effect (P=0.035, η2=0.031) of the CYP2C19*17 genotype on imipramine+desipramine concentrations. Although the CYP2C19*17 allele is associated with a significantly increased metabolism of imipramine, CYP2C19*17 genotyping will, in our view, not importantly contribute to dose management of patients on imipramine therapy guided by imipramine+desipramine plasma concentrations.
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Acknowledgements
Part of this work was supported by an internal grant (Erasmus MC Revolving Fund, Top-Down, MEC 194.305/2000/168B).
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Schenk, P., van Vliet, M., Mathot, R. et al. The CYP2C19*17 genotype is associated with lower imipramine plasma concentrations in a large group of depressed patients. Pharmacogenomics J 10, 219–225 (2010). https://doi.org/10.1038/tpj.2009.50
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DOI: https://doi.org/10.1038/tpj.2009.50
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