Survey of the Utility of Genetic Polymorphisms for the Development of Individualized Tacrolimus Administration under the Co-administration of Letermovir

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16078
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Kyushu University
• Principal Investigator: Suetsugu Kimitaka 九州大学, 大学病院, 副薬剤部長 (50867330)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: レテルモビル / 抗真菌薬 / タクロリムス / 遺伝子多型 / 母集団薬物動態解析

Outline of Final Research Achievements

Population pharmacokinetic analysis showed that the co-administration of letermovir resulted in an increase of 1.72 times in the Vmax (maximum reaction rate) of voriconazole and a 44% decrease in the median blood concentration of voriconazole in hematopoietic cell transplantation. No influence was observed in regard to CYP2C19 genetic polymorphisms in this study.
Furthermore, factors affecting the blood concentration of posaconazole were identified using population pharmacokinetic analysis, and the effect of these factors on the achievement rate of the target blood concentration of posaconazole was investigated. As a result, it was found that body weight, total protein levels, and diarrhea were factors that caused variations in the blood concentration. It can be speculated that in patients with a high body weight, hypoalbuminemia, or diarrhea, the target blood concentration of posaconazole may fall below the level specified in the package insert.

Free Research Field

臨床薬理学

Academic Significance and Societal Importance of the Research Achievements

レテルモビルは、2018年3月にサイトメガロウイルス感染症の抑制を目的に本邦で承認され、造血細胞移植後に広く使用されるようなった。一方、レテルモビルは薬物間相互作用が多く報告されており、アゾール系抗真菌薬との相互作用の結果、タクロリムスの血中濃度にも影響を与える可能性が考えられた。また、遺伝子多型は人種差の影響も受けるため、本邦での結果が重要である。本研究では、アゾール系抗真菌薬との相互作用について、母集団薬物動態解析を用いて、ボリコナゾールとポサコナゾールにおける影響を明らかにした。本研究は、レテルモビル併用下における抗真菌薬、タクロリムスの個別化投与の発展に向けた重要な成果と考えられる。