Effects of CYP2D6 Genotypes on Venlafaxine Metabolism in Japanese Psychiatric Patients With Depression.
| Autor: | Komahashi-Sasaki H; Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu-machi, Shimotsuga., Yasui-Furukori N; Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu-machi, Shimotsuga., Sasaki T; Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu-machi, Shimotsuga., Shinozaki M; Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu-machi, Shimotsuga., Hayashi Y; Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu-machi, Shimotsuga., Kato K; Sakura La Mental Clinic, Utsunomiya, Tochigi; and., Inoue Y; Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu-machi, Shimotsuga., Tsuchimine S; National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan ., Watanabe T; Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu-machi, Shimotsuga., Sugawara N; Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu-machi, Shimotsuga., Shimoda K; Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu-machi, Shimotsuga. |
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| Jazyk: | angličtina |
| Zdroj: | Therapeutic drug monitoring [Ther Drug Monit] 2021 Oct 01; Vol. 43 (5), pp. 681-687. |
| DOI: | 10.1097/FTD.0000000000000854 |
| Abstrakt: | Background: Venlafaxine (VEN) is primarily metabolized by CYP2D6. Although several studies have reported the significant effects of CYP2D6 on VEN and O-desmethylvenlafaxine (ODV) pharmacokinetics in Whites, limited data are available regarding the effects of the Asian-specific CYP2D6 genotype on VEN metabolism. This study evaluated the effects of the CYP2D6*10 and CYP2D6*5 genotypes on the steady-state plasma concentrations of VEN and ODV in Japanese patients. Methods: This study included 75 Japanese patients with depression who were treated with VEN. Steady-state plasma concentrations of VEN and ODV were measured using liquid chromatography. Polymerase chain reaction was used to determine CYP2D6 genotypes. A stepwise multiple regression analysis was performed to analyze the relationship between independent variables (sex, age, smoking habit, and number of mutated alleles, CYP2D6*10 and CYP2D6*5), subject-dependent variables (plasma concentrations of VEN and ODV [all corrected for dose and body weight]), and the ODV/VEN ratio. Results: Significant correlations were observed between the daily dose of VEN (corrected for body weight) and plasma concentrations of VEN (r = 0.498, P < 0.001) and ODV (r = 0.380, P = 0.001); ODV plasma concentrations were approximately 3.2 times higher than VEN plasma concentrations (VEN versus ODV = 18.60 ng/mL versus 59.10 ng/mL). VEN plasma concentrations (corrected for dose and body weight) did not differ with differing numbers of CYP2D6-mutated alleles. However, the ODV/VEN ratio decreased as the number of mutated CYP2D6 alleles increased (P = 0.001). Conclusions: This is the first study to examine the effects of CYP2D6*10 in a clinical setting. Although no effects on the plasma concentrations of VEN or ODV were observed, CYP2D6 polymorphism affects the ODV/VEN ratio. Further studies are needed to confirm the clinical relevance of these findings. Competing Interests: N. Yasui-Furukori has been a speaker for Otsuka Pharmaceutical Co. Ltd., Mochida Pharmaceutical Co. Ltd., Dainippon Sumitomo Pharmaceutical Co., and MSD Co. K. Shimoda has received research support from Novartis Pharma K.K., Dainippon Sumitomo Pharma Co., Astellas Pharma Inc., Meiji Seika Pharma Co. Ltd., Eisai Co. Ltd., Pfizer Inc., Otsuka Pharmaceutical Co. Ltd., Daiichi Sankyo Co., and Takeda Pharmaceutical Co. Ltd., and honoraria from Eisai Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co. Ltd., Meiji Seika Pharma Co. Ltd., Janssen Pharmaceutical K.K., Shionogi & Co. Ltd., Dainippon Sumitomo Pharma Co., Daiichi Sankyo Co., and Pfizer Inc. The funders did not have any role in data collection or in the study design, analysis, decision to publish, or preparation of the manuscript. The remaining authors declare no conflict of interest. (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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