Identification of factors contributing to intra- and inter-patient variability in blood concentrations of immunosuppressive drugs

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K14974
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: University of Tsukuba
• Principal Investigator: Suzuki Yoshiharu 筑波大学, 附属病院, 臨床講師(病院) (80760298)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 免疫抑制薬 / 薬物代謝酵素 / 薬物間相互作用 / 遺伝子多型 / 個体内変動

Outline of Final Research Achievements

Tacrolimus is used as an immunosuppressive agent for allograft transplantation and requires frequent measurements of the blood concentration due to the narrow therapeutic range. To avoid graft-versus-host diseases and tacrolimus-related toxicities, conducting therapeutic drug monitoring of tacrolimus is important for optimizing the dose keeping the therapeutic range of the blood concentration in individual patients. This study found that CYP3A5 and POR gene polymorphisms are inter-individual tacrolimus variation factors in renal transplant recipients. In the aspect of intra-individual variability, this study also indicated that vonoprazan coadministration increases the tacrolimus concentration regardless of CYP2C19 or CYP3A5 genetic polymorphisms. Thus, it is considered that frequent therapeutic drug monitoring of tacrolimus is necessary when intra-individual variabilities of tacrolimus blood concentrations are suspected.

Free Research Field

臨床薬理学

Academic Significance and Societal Importance of the Research Achievements

タクロリムス血液中濃度の変動には、遺伝子多型による個体間変動だけではなく、併用薬の変更や生理的因子の変化による個体内変動にも注意を配る必要がある。本研究では、タクロリムス血液中濃度の個体間および個体内変動について、臨床的な観点から情報の蓄積ができたと考える。一方で、生理的因子の変化がタクロリムス血液中濃度に与える影響は不明な点が多い。患者状態によって生じる生理的変化を避けることは困難であり、生理的因子の変化がタクロリムス血液中濃度に与える影響を明らかにできれば、タクロリムス血液中濃度コントロールを介して移植臓器の生着率向上に寄与できることが期待される。