2017 Fiscal Year Final Research Report
Pharmakokinetic-pharmacodynamic analysis of cisplatin with hydration and mannitol diuresis
Project/Area Number |
15K18941
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Medical pharmacy
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Research Institution | Kobe Gakuin University |
Principal Investigator |
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Keywords | シスプラチン / 腎障害 / 強制利尿法 / PKPD解析 |
Outline of Final Research Achievements |
Forced diuresis treatment did not significantly alter the plasma cisplatin pharmacokinetics but dramatically decreased the urine concentration of unbound cisplatin and its accumulation into the kidneys in a dose-dependent manner, and correspondingly, nephrotoxicity was dose-dependently attenuated by forced diuresis. The pharmacokinetic-pharmacodynamic analysis suggested that the urine cisplatin concentration has a comparable impact on the cisplatin-induced nephrotoxicity to that in plasma, probably owing to the reabsorption of cisplatin from urine, which can be attenuated by forced diuresis. These results indicated that the nephroprotective effect of forced diuresis is a pharmacokinetic-based drug-drug interaction possibly due to the inhibition of cisplatin reabsorption from urine. Monitoring of urine cisplatin concentration may lead to the optimization of a forced diuresis protocol with mannitol.
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Free Research Field |
薬物動態
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