PK-PD analysis for aprepitant personalized dose adjustment to optimize individualized antiemetic therapy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K21226
• Project/Area Number (Other): 18H06108 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Kyushu University
• Principal Investigator: Katsube Yurie 九州大学, 大学病院, 薬剤師 (10827223)
• Project Period (FY): 2018-08-24 – 2022-03-31
• Keywords: 白金系抗癌剤による悪心・嘔吐 / サブスタンスP / アプレピタント

Outline of Final Research Achievements

Oral administration of aprepitant, NK-1 receptor antagonists, is essential to give cancer patients releasing from chemotherapy-induced nausea and vomiting (CINV). However, in some patients, CINV is not well controlled. Therefore, in this study, we aimed to develop and apply the concentration of salivary substance P (SP), a ligand for the NK1 receptor, as non-invasive biomarker with LC-MSMS.The results showed that LC-MSMS could detect SP in the order of pg/mL, which is comparable to ELISA analysis, but SP in saliva collected from healthy subjects was below the detection limit. The maximum concentration of SP in saliva was 1200 pg/mL in ELISA analysis using the same subject, suggesting that SP is present in saliva at lower concentration than the previously reported concentration by ELISA analysis, and that it is necessary to search for alternative markers for SP.

Free Research Field

薬物トランスポーター　薬物代謝酵素　薬物動態　医療薬学

Academic Significance and Societal Importance of the Research Achievements

SPの脱NH3化やリン酸化といった定量分析における課題は残るものの、本研究においてSPは既報において報告されるより低い微量濃度で生体試料中に存在することが明らかとなった。SPと共通アミノ酸配列を有するタキキニンペプチドとの交差反応性の高さがELISA分析において問題視されてきたが、どの程度結果に影響を及ぼすかこれまで明らかにされていなかった。現時点においてSPのCINVのバイオマーカーとしての実現性は低いものの、ELISA分析を用いた唾液中のSPと嚥下能との関連性は数多く報告されており、本研究結果は既報における疾患との関連性が高いと考えられてきた末梢中のSPの解釈に一石を投じる結果である。