Pharmacokinetic analysis of the fetus for doxorubicin administration during pregnancy

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06761
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Hoshi University
• Principal Investigator: Wataru Ochiai 星薬科大学, 薬学部, 教授 (40381008)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 妊娠 / 抗癌剤 / リポソーム製剤 / ドキソルビシン / DOXIL

Outline of Final Research Achievements

To confirm the safety of using doxorubicin during pregnancy, it was analyzed from a pharmacokinetic point of view. After administering doxorubicin to mice in the second trimester and analyzing the time course and distribution of the amount of doxorubicin transferred from the mother to the fetus, when her doxorubicin was administered to pregnant mice, it was present in the fetus at a high concentration immediately after administration. It was. In the fetus 24 hours after doxorubicin administration, the concentration was high in the brain, liver and gastrointestinal tract. In addition, children born to mothers who received doxorubicin were significantly stunted. Furthermore, in this study, we focused on the liposome preparation DOXIL of doxorubicin and verified its usefulness, and found that it has low transferability to the fetus.

Free Research Field

薬物動態

Academic Significance and Societal Importance of the Research Achievements

妊娠マウスへのDOXIL投与は、doxorubicin に比べて、胎児への移行が少なく、産まれた後も子供の発育もコントロール（生理食塩水）と変わらないことから、安全な製剤になりうることを示唆された。一方、妊娠中にdoxorubicin を投与する場合には、24 時間後までの胎児中 doxorubicin 濃度が、その後の胎児の生存率や発育に影響を及ぼすことが考えられるため、この間の胎児中の doxorubicin 濃度をコントロールできれば、胎児への毒性（影響）を軽減できる可能性も示唆された。