2019 Fiscal Year Final Research Report
Effect of arrhythmia control by amiodarone on the pharmacokinetics of immunosuppressants in heart transplant patients.
| Project/Area Number |
17K08476
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Kobe Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 非アルコール性脂肪肝炎（NASH） / アミオダロン塩酸塩 / 薬物動態 |
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| Outline of Final Research Achievements |
Adverse events of amiodarone-induced NASH were examined using spontaneous adverse event database. We showed that positive signal detection for amiodarone-associated NASH, and those data suggested that amiodarone are strongly associated with an increased risk of NASH. In addition, the expression of drug-metabolizing enzymes and transporters associated with bile transport were reduced in the liver of mice with NASH. These results indicate the possible dysfunction of drug metabolism and enterohepatic circulation in the NASH. We showed that this mechanism is likely associated with disruption of small intestinal barrier function.
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| Free Research Field |
医療薬学
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| Academic Significance and Societal Importance of the Research Achievements |
心臓移植後の拒絶反応の防止を目的として使用されるシクロスポリンとタクロリムスは肝臓と小腸でCYP3Aによる代謝を受け、胆汁中に排泄される。ミコフェノール酸モフェチルは腸肝循環する。つまり、NASHでは、肝臓での薬物代謝機能の低下および肝臓と小腸での胆汁の循環障害により免疫抑制剤の体内動態が変動することが予想される。しかし、心臓移植前のアミオダロンの投与が心臓移植後の免疫抑制剤の治療に及ぼす影響については明らかにされていない。すなわち、本研究成果は、心臓移植後の免疫抑制剤による適正な薬物療法の推進に貢献する。
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