| Project/Area Number |
60460219
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Faculty of Pharmaceutical Sciences, Kanazawa University |
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Principal Investigator |
MIYAZAKI Motoichi Faculty of Pharmaceutical Sciences, Kanazawa University, 薬学部, 教授 (50009164)
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| Co-Investigator(Kenkyū-buntansha) |
KIZU Ryoichi Faculty of Pharmaceutical Sciences, Kanazawa University, 薬学部, 教務職員 (80143915)
OKUBO Noboru Faculty of Pharmaceutical Sciences, Kanazawa University, 薬学部, 助手 (30115216)
HAYAKAWA Kazuichi Faculty of Pharmaceutical Sciences, Kanazawa University, 薬学部, 助教授 (40115267)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1986: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | biologically active substances / anticaner agent / platinum complex / cis-diamminedichloroplatinum(II) / (trans-1-1,2-diaminocyclohexane)oxalatoplatinum(II) / high performance liquid chromatography / sensitive determination method / 体内動態 |
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| Research Abstract |
Recently, platinum complexes have attracted much attention for their biological activities, especially anticancer ones. cis-Diamminedichloroplatinum(II) ( CDDP ) has been clinically adopted and is the most fundamental key compound among the anticancer platinum complexes. In this study, metabolism of CDDP, especially of the intact species of CDDP which is considered as the main species in antineoplastic action of CDDP, was investigated in rabbits to get further understanding on the pharmacokinetic behavior and biological activities of platinum complexes. Results obtained in this study are as follows. 1. A high performance liquid chromatographic method for determining CDDP in plasma and urine was developed by applying column-switching technique and detection at 210nm. A photodiodearray spectrophotometric detector ( a Shimadzu SPD-MlA ) afforded by the present grant was effective for accurate determination of CDDP. 2. Remarkable changes in pharmacokinetics of CDDP were found in rabbits administered CDDP and sodium thiosulfate which is an effective agent to reduce toxic side effects of CDDP. These changes will be important to explain the effect of sodium thiosulfate to reduce the toxic effects of CDDP. 3. It was found that CDDP and (trans-1-1,2- diaminocyclohexane)oxalatoplatinum(II) which is considered as one of the promising anticancer platinum complexes significantly differed in the rate of urinary excretion of intact species.
This study will offer a bigining of forthcoming investigations on relationships between the pharmacokinetics and the biological activities of platinum complexes. Studies on this field will be further extended.
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