The development of optimal individualized therapy based on PK/PD/PGx using the DBS method in community pharmacies and at home

Research Project

Project/Area Number	18K14990
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 47060:Clinical pharmacy-related
Research Institution	Keio University
Principal Investigator	Yokoyama Yuta 慶應義塾大学, 薬学部(芝共立), 助教 (70725796)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	TDM / hemaPEN / 赤血球／血漿移行定数 / DBS / PK/PD/PGx / 微量血液 / 遺伝子多型解析 / テオフィリン / K濃度 / ヘマトクリット値 / ヘマトクリットHt値 / POCT
Outline of Final Research Achievements	The dried blood spot (DBS) method is recommended for therapeutic drug monitoring (TDM) and genetic polymorphism analyses because the microsampling approach involved is simple and minimally invasive. In the present study, we established a method for measuring drug concentrations and analyzing genetic polymorphisms in a small amount of whole blood using DBS sampling. We also demonstrated the validity of the method to convert whole blood concentrations to plasma concentrations in the DBS method using K+ concentrations on the DBS card and the RBC/plasma rate. The establishment of the method to convert whole blood concentrations to plasma concentrations in DBS will contribute to the development of an individual optimized dosage regimen that considers efficacy and safety based on PK/PD/PGx using DBS, which will facilitate TDM in community pharmacies and at home.
Academic Significance and Societal Importance of the Research Achievements	簡便かつ低侵襲な微量採血によるdried blood spot（DBS）カードの活用が血中濃度のモニタリングおよび遺伝子多型解析の実施において推奨されている。本研究により微量血液を用いるDBS法による薬物濃度の測定および遺伝子多型の解析を確立し、DBSカードの薬物濃度から治療に関係する薬物濃度への換算法の妥当性を明らかとした。今後、DBSカードを用いて有効性および安全性を考慮した最適な投与方法の構築に繋がる事で薬局・居宅における血中濃度のモニタリングに向けても期待できる。