The elucidation of the causal relationship between fetal accumulation of ritodrine and the development of neonatal hypoglycemia

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22703
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Kanazawa University
• Principal Investigator: FUJITA ARIMI 金沢大学, 附属病院, 特任助教 (50876026)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: リトドリン / 新生児低血糖症 / 胎盤透過

Outline of Final Research Achievements

In this study, clinically relevant animal models was developed to clarify the causal relationship between the placental permeability and fetal accumulation of ritodrine and neonatal hypoglycemia. No neonatal hypoglycemia was observed in a model in which ritodrine 8 mg/kg/day was administered subcutaneously for 7 days, but significant hypoglycemia persisted in neonates in a model in which 16 mg/kg/day was administered intravenously rapidly to the mother. Neonatal plasma ritodrine concentrations remained 10-fold higher in the rapid IV model. These results indicate that fetal plasma ritodrine concentrations at the time of cesarean section are higher than those during fetal ritodrine exposure, and that ritodrine-induced neonatal hypoglycemia may develop when neonatal ritodrine concentrations remain at high levels.

Free Research Field

薬物動態

Academic Significance and Societal Importance of the Research Achievements

切迫早産は妊婦の約30%に生じ、早産児は重篤な障害が出現する可能性が高くなるため切迫早産管理は重大な課題である。リトドリンは切迫早産に適応を持つ唯一の薬剤であるが、新生児低血糖症といった重大な副作用を有するため慎重な使用が求められている。本研究は新生児低血糖症発症と新生児血漿中リトドリン濃度との関係性を示したものである。また、本研究では母体と胎児でのリトドリン血漿中濃度比も算出しており、新生児でのリトドリン血漿中濃度予測を行う端緒となる成果を得た。本研究成果は新生児毒性を加味した切迫早産薬物治療の適正化に繋がる。