Mechanism-Based Pharmacokinetic-Pharmacodynamic Modeling of Drug-Induecd Dysglycemia

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08394
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Nagata Masashi 東京医科歯科大学, 医学部附属病院, 准教授 (40412829)
• Research Collaborator: MASATO Yasuhara
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 副作用 / 血糖値 / クロザピン / アドレナリン

Outline of Final Research Achievements

Clozapine, an atypical antipsychotic agent, has been reported to cause acute hyperglycemia. However, the mechanism of clozapine-induced rapidly developing hyperglycemia is not well elucidated. To clarify the mechanism underlying clozapine-induced acute hyperglycemia, we investigated the effects of single intravenous administration of clozapine on the serum concentrations of glucose and several endogenous substances in rats.
The serum concentrations of glucose increased after the injection of clozapine. Compared to our previous study using olanzapine, not only adrenaline but also glucagon increased significantly following a single administration of clozapine. These results suggest that not only adrenaline but also glucagon is associated with clozapine-induced elevations in blood glucose levels, and the mechanism responsible for the induction of hyperglycemia following a single injection of clozapine may differ from that by olanzapine.

Free Research Field

医療薬剤学

Academic Significance and Societal Importance of the Research Achievements

薬物により引き起こされる高血糖や低血糖は、患者の生命にも関わる重大な副作用であり、これらの血糖値異常の副作用が、臨床使用の妨げとなる薬物も少なくない。これらの薬物を安全に使用するためには、血糖値異常のメカニズムの全容を明らかにし、個別の患者における血糖値異常の予測や予防法の開発につなげることである。本研究により、非定型抗精神病薬による血糖値異常のメカニズムを明らかにすることができ、今後の薬物療法の安全性の向上に大きく貢献するものと期待される。