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. 2018 Jun;40(3):356-361.
doi: 10.1097/FTD.0000000000000506.

Effects of Cytochrome P450 (CYP) 2C19 Genotypes on Steady-State Plasma Concentrations of Escitalopram and its Desmethyl Metabolite in Japanese Patients With Depression

Shoko Tsuchimine  1   2 , Shinichiro Ochi  3 , Misuzu Tajiri  4 , Yutaro Suzuki  4 , Norio Sugawara  1   5 , Yoshimasa Inoue  1 , Norio Yasui-Furukori  1
Affiliations

Effects of Cytochrome P450 (CYP) 2C19 Genotypes on Steady-State Plasma Concentrations of Escitalopram and its Desmethyl Metabolite in Japanese Patients With Depression

Shoko Tsuchimine et al. Ther Drug Monit. 2018 Jun.

Abstract

Background: Plasma concentrations of the S-enantiomer of citalopram were different between extensive and poor CYP2C19 metabolizers in healthy subjects and depressed patients. However, most studies applied dose-corrected concentrations. Thus, we studied the effects of polymorphisms of the CYP2C19 gene on raw plasma drug concentrations in Japanese patients with depression.

Methods: Subjects in this study consisted of 412 depressed patients receiving 5, 10, 15, or 20 mg of escitalopram once a day. Plasma concentrations of escitalopram and desmethylescitalopram were quantified using HPLC. CYP2C19 genotypes were identified using polymerase chain reaction methods.

Results: There were no differences in the steady-state plasma concentrations of escitalopram or desmethylescitalopram in each dose group (5, 10, 15, or 20 mg of escitalopram) among CYP2C19 genotype groups. However, 1-way analysis of variance showed significant effects of CYP2C19 genotypes on the dose-adjusted plasma concentration of escitalopram but not in the dose-adjusted plasma concentration of desmethylescitalopram. Analysis of covariance including age, sex, and body weight showed significant effects of CYP2C19 genotypes on the dose-adjusted plasma concentration of escitalopram and the ratio of desmethylescitalopram to escitalopram.

Conclusions: These findings suggest that the CYP2C19 variants are associated with steady-state plasma concentrations of escitalopram to some extent but are not associated with desmethylescitalopram.

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Conflict of interest statement

N. Yasui-Furukori has received grant/research support or honoraria from and has been on the panels of Dainippon, Mochida, MSD. The remaining authors declare no conflict of interest.

Figures

FIGURE 1.
FIGURE 1.
Influence of CYP2C19 genotypes on the steady-state plasma concentration of escitalopram in each dose with box-and-whisker plots.
FIGURE 2.
FIGURE 2.
Influence of CYP2C19 genotypes on the steady-state plasma concentration of desmethylescitalopram in each dose, with box-and-whisker plots.
FIGURE 3.
FIGURE 3.
Influence of CYP2C19 genotypes on the steady-state plasma concentration of escitalopram adjusted by dose, with box-and-whisker plots.
FIGURE 4.
FIGURE 4.
Influence of CYP2C19 genotypes on the steady-state plasma concentration of escitalopram adjusted by dose, with box-and-whisker plots.
See this image and copyright information in PMC

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