2019 Fiscal Year Final Research Report
Development of antimicrobial chemotherapy based on clinical pharmacometrics and maturation
| Project/Area Number |
17K08438
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Nihon University (2019)
University of Toyama (2017-2018) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山本 善裕 富山大学, 学術研究部医学系, 教授 (70452844)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | クリニカルファーマコメトリクス / 成熟度 / ファーマコキネティクス / ファーマコロジー / C-反応性たんぱく / 血小板 |
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| Outline of Final Research Achievements |
The teicoplanin concentration producing 50% of the maximum inhibition of CRP production was estimated to be 2.66 mg/L. Cmin of teicoplanin in patients with higher loading doses (15 mg/kg) reached the target range (15-30 mg/L) with a probability of >50% in the dosing simulation. We described the influence of body size, body composition and renal function on pharmacokinetics of teicoplanin. Body weight (WT) and maturation of body function were significant covariates for pharmacokinetics of linezolid in pediatric patients. The elimination half-life of linezolid in a pediatric patient with a WT of 9.9 kg and age of 24 months (median of this study) was 3.0 h. Thrombocytopenia was detected in three patients (21.4%), and the minimum concentrations (Cmin) in these patients were significantly higher than those in patients without thrombocytopenia (P < 0.05).
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| Free Research Field |
臨床薬物動態学
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| Academic Significance and Societal Importance of the Research Achievements |
重症感染症治療薬は優れた抗菌効果を示す反面、薬物動態および薬力学には個体差が大きく、血液毒性等の副作用発現により、投与を中止する場合も多い。一方、体脂肪は薬物の体内分布に大きな影響を及ぼすことも知られている。日本人は世界的に見ても肥満率・体脂肪率が極端に低いため、海外の投与量をそのまま日本人に当てはめた場合、薬物が脂肪に分布できず、みかけの分布容積が低下し、血中薬物濃度が上昇し副作用を発現する。本研究成果は様々な病態、成長・体格差および生体生理機能に対する化学療法の個別化に資するものと考えられる。
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