Clinical implication of lipoprotein-binding in therapeutic drug monitoring of amiodarone

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07188
• 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: University of Tsukuba
• Principal Investigator: Doki Kosuke 筑波大学, 医学医療系, 准教授 (90620881)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: アミオダロン / リポタンパク質

Outline of Final Research Achievements

Amiodarone, an anti-arrhythmic drug, is highly distributed to serum lipoproteins such as very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), which are the carriers of triglyceride and cholesterol. This study aimed to investigate the association of serum concentrations of amiodarone with the levels of serum lipids in terms of drug distribution to lipoprotein fractions in patients with hyperlipidemia. Serum amiodarone concentration positively correlated with the level of serum triglyceride and was higher in the hypertriglyceridemic state than in normotriglyceridemic state. In the hypertriglyceridemic state, the distribution of amiodarone increased in LDL/VLDL fraction. The results of this study reveal that serum concentrations of amiodarone increase in the hypertriglyceridemic state through the increased lipoprotein-binding. This finding may help constructing the effective amiodarone therapeutic drug monitoring.

Free Research Field

臨床薬理学

Academic Significance and Societal Importance of the Research Achievements

アミオダロンを用いた不整脈治療では、間質性肺炎などの致死的な心外性副作用の発現により治療の継続がしばしば困難となる。しかし、アミオダロンの副作用は血清中の総アミオダロン濃度（結合型+非結合型）との関連性が乏しく、その予測は難しい。本研究で明らかになった高トリグリセリド値の患者における血清中アミオダロン濃度の増加を考慮することが、アミオダロンの副作用モニタリング法の構築に役立つ可能性がある。