2023 Fiscal Year Final Research Report
Mechanisms for the pharmacokinetic variability in patients with right-sided heart failure: A longitudinal data analysis for optimization of the dosage regimen.
| Project/Area Number |
21K06687
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 47060:Clinical pharmacy-related
|
|---|
| Research Institution | University of Toyama |
|---|
Principal Investigator |
TAGUCHI MASATO 富山大学, 学術研究部薬学・和漢系, 教授 (20324056)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
市田 蕗子 国際医療福祉大学, 臨床医学研究センター, 特任教授 (30223100)
廣野 恵一 富山大学, 学術研究部医学系, 講師 (80456384)
|
|---|
| Project Period (FY) |
2021-04-01 – 2024-03-31
|
| Keywords | optimum dosage / longitudinal data / developmental change / congenital heart disease / right heart failure / intestinal permeability |
|---|
| Outline of Final Research Achievements |
We have developed a new pharmacokinetic analysis method that enables sensitive detection of the covariates of the pharmacokinetics by longitudinal data analysis including the developmental change in childhood. In this study, we successfully demonstrated that longitudinal data obtained from the same case in the drug efficacy and pharmacokinetic analysis were useful for the detection of covariates in the pharmacokinetic studies of warfarin and caffeine. In addition, it was suggested that in children with congenital heart disease complicated by right heart failure, drug absorption in the gastrointestinal tract was increased by unknown mechanism. We found that the intestinal permeability of polyethylene glycol (PEG400) was significantly enhanced in rats that developed right heart failure secondarily due to monocrotaline-induced pulmonary arterial hypertension.
|
| Free Research Field |
医療薬学
|
| Academic Significance and Societal Importance of the Research Achievements |
長期データを積極的に活用しようとする取り組みは国内外を通じても例がほとんどない。新生児・小児期の身体発達に伴う薬物動態変動は倫理的制約から直接評価することが非常に困難であるため、近年では生理学的薬物速度論（PBPK）モデルに基づくシミュレーション解析が進んでいるが、右心不全など特殊な患者集団では現存する数理モデルの適合性が必ずしも良い保証がない。少数採血デザインを発展させた本研究のデータ解析法は、小児・新生児を対象とする薬物動態試験に先駆的役割を果たすとともに、小児発達と薬物動態変動に関する知見の醸成を促し、得られる成果は臨床薬理学・薬物動態学の進歩に寄与するものと期待される。
|
