Mechanism underlying potentiated pharmacological effects of sedatives with renal failure

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K08097
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Okayama University
• Principal Investigator: AIBA TETSUYA 岡山大学, 医歯薬学総合研究科, 准教授 (00231754)
• Co-Investigator(Kenkyū-buntansha): 北村 佳久 岡山大学, 大学病院, 准教授 (40423339)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 投与設計 / 個別化医療 / 腎不全 / 中枢神経系 / PK/PD

Outline of Final Research Achievements

Pharmacological potency of therapeutic compounds alters in patients with severe disease, in which it is known that besides the affected organ, non-affected organs that are not immediately connected with the disease respond to therapeutic compounds in an altered manner. To clarify mechanism underlying the altered response, we examined the potentiation of the pharmacological effects of sedatives in rats with experimentally induced renal failure. It was demonstrated that the cerebral expression of chloride transporter protein alters with renal failure, suggesting that cellular regulation regarding chloride concentration alters with renal failure to allow the action potential in the nerve cells to be more effectively suppressed.

Free Research Field

臨床薬物動態学

Academic Significance and Societal Importance of the Research Achievements

薬物療法の個別化至適化は、患者疾病の迅速な回復と生活の質の向上に資することに加え、医療費や社会保障費の削減に帰することにおいて重要である。今回の研究成果は、薬物の治療効果が患者の全身状態の変化によって変動すること、そしてその変動が薬の標的部位の感受性変化に因ることを明らかにしたものである。薬物感受性の変化に応じて患者毎に治療薬の処方量を調節することで、これまで以上に効果的な薬物療法の個別化至適化の実施が可能である。