Pharmacogenomic study for optimizing dosage of antipsychotic drugs based on individual genetic polymorphism

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07490
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Fujita Health University
• Principal Investigator: Saito Takeo 藤田医科大学, 医学部, 講師 (30767611)
• Co-Investigator(Kenkyū-buntansha): 池田 匡志 名古屋大学, 医学系研究科, 教授 (60424933)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 抗精神病薬 / ファーマコゲノミクス / 薬物血中濃度

Outline of Final Research Achievements

The aim of this study was to examine the relationship between blood concentrations of antipsychotics and drug metabolizing enzyme genotypes, and to establish a basis for predicting individual optimal doses of antipsychotics. We measured the blood concentrations of clozapine and norclozapine in patients with schizophrenia and conducted association analyses between these concentrations and drug metabolizing enzyme genotypes and single nucleotide polymorphisms (SNPs). The results showed no significant associations between drug metabolizing enzyme genotypes or SNPs and clozapine blood concentrations, norclozapine blood concentrations, or the clozapine/norclozapine concentration ratio. However, it cannot be ruled out that this result may be due to low detection power caused by insufficient sample size. Therefore, further analyses with an expanded sample size are necessary.

Free Research Field

精神医学

Academic Significance and Societal Importance of the Research Achievements

本研究においてクロザピン血中濃度や代謝に有意に関連するPK関連遺伝子型、あるいはSNPは見出されなかった。しかし、この結果はサンプル数不足による検出力の低さに由来する可能性が否定できず、今後もサンプル数を拡大した解析が必要である。その結果、関連する遺伝子型が見出されれば、その遺伝子型の情報を用いることで、個人の至適用量を予測しうる可能性がある。このため、今後も本研究と同様の手法を用いた研究の継続が必要であると考える。