2023 Fiscal Year Final Research Report
Pharmacokinetic analysis of venlafaxine focusing on CYP gene polymorphisms
Project/Area Number |
20K16052
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 47060:Clinical pharmacy-related
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Research Institution | Dokkyo Medical University |
Principal Investigator |
Sasaki Hazuki 獨協医科大学, 医学部, 助教 (10831480)
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Project Period (FY) |
2020-04-01 – 2024-03-31
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Keywords | venlafaxine / CYP2D6 / pharmacokinetics / pharmacogenetics |
Outline of Final Research Achievements |
Venlafaxine (VEN) is mainly metabolized by CYP2D6 to O-desmethylvenlafaxine (ODV), also known as desvenlafaxine, which is under development in Japan. Therefore, we believe it is necessary to study the disposition of both VEN and ODV in order to analyze the antidepressant effect of VEN administration. Plasma concentrations of VEN and its metabolites were measured in approximately 70 Japanese patients with depression and factors affecting VEN metabolism, including CYP2D6 gene polymorphisms, were investigated. A significant correlation was observed between the body weight-corrected daily dose of VEN and plasma concentrations of VEN and its metabolite, ODV, with plasma concentrations of ODV being higher than those of VEN. Although dose- and weight-corrected VEN plasma concentrations did not differ among different numbers of CYP2D6 mutant alleles, the ODV/VEN ratio decreased with increasing numbers of CYP2D6 mutant alleles, indicating that the metabolism rate is altered.
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Free Research Field |
臨床精神薬理学
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Academic Significance and Societal Importance of the Research Achievements |
Venlafaxine (VEN)は欧米では20年以上の使用歴があるものの、日本では2015年に使用開始となったばかりである。白人におけるVENおよびODVの薬物動態にCYP2D6が大きく影響することはいくつかの研究で報告されているが、アジア人特有のCYP2D6遺伝子型がVENの代謝に及ぼす影響については、限られたデータしかない。 本研究では、VENで治療を受けたうつ病を伴う日本人精神疾患患者75名を対象に、VEN、ODVの血漿中濃度を測定し、CYP2D6*10及びCYP2D6*5アリルが日本人患者のVEN及びODVの定常血中濃度に及ぼす影響について検討した。
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