1988 Fiscal Year Final Research Report Summary
Studies on the Metabolism of Biologically Active Platinum Complexes
| Project/Area Number |
62570962
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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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, 助的 (80143915)
OKUBO Noboru Faculty of Pharmaceutical Sciences, Kanazawa University, 薬学部, 助手 (30115216)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Biologically Active Substances / Anticancer Agent / Platinum Complex / cis-Diamminedichloro-platinum(II) / Pharmacokinetic Behavior / Toxic Side Effect / Nephrotoxicity / チオ硫酸ナトリウム |
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| Research Abstract |
Cisplatin(CDDP), one of the biologically active platinum complexes, is a potent anticancer drug. Recently, sodium thiosulfate(STS) has attracted much attention for its effects to reduce toxic side effects of CDDP. Although STS has been considered to react CDDP and/or its metabolites to produce the biologically inactive compounds in the body, no invetigation on CDDP-STS reaction products has been undertaken. The authors reported that three species containing platinum(designated as P1,P2 and P3) were found in the reaction mixture of CDDP and STS. In this study, pharmacokinetic behavior of P2 and P3 was studied to get further insight on the chemical species of platinum and their activities after administration of CDDP. Results obtained in this study are as follows. 1. P2 and P3 were isolated and purified. Their elemental analysis indicated that P2 and P3 were cis-diamminedithiosulfatoplatinum(II) and amminetris(thiosulfato)platinum(II), respectively. 2. A high performance liquid chromatographic method for determining P2 and P3 in plasma and urine was developed by applying post-column reaction and fluoresence detection based on reduction of cerium(IV) to cerium(III) by thiosulfate. 3. P2 and P3 were found in plasma and urine of rabits intravenously injected with CDDP and STS. It was found that P2 and P3 were major reaction products in the body and had larger renal clearances than filterable platinum in plasma. These results indicate that kinetic behavior of P2 and P3 in the body is important to explain the effect of STS to reduce the toxic side effects of CDDP.
Knowledge on the chemical structures and pharmacokinetic behavior of CDDP-STS reaction products in the body was obtained for the first time. This study will offer a bigining of forthcoming investigations on relationships between the pharamacokinetics and biological activities of platinum complexes.
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