Investigation of transporter-mediated interaction between cisplatin and silver sulfadiazine in rats

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  • ラットにおけるシスプラチンとスルファジアジン銀のトランスポーターを介した相互作用の検討
  • ラット ニ オケル シスプラチン ト スルファジアジンギン ノ トランスポーター オ カイシタ ソウゴ サヨウ ノ ケントウ

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Cisplatin (CDDP) is a platinum complex and is used for treatment of solid tumors. CDDP administered intravenously is ingested into the cells by copper transporter 1 (CTR1). Silver sulfadiazine (AgSD) is a topical antibiotic that prevent wound infection. Ag is reported to inhibit the mechanism of CTR1. We examined transporter-mediated drug-drug interaction using CDDP and AgSD in rats. The serum concentrations of platinum in blood and in kidney and liver tissues were measured. A blood test was performed to observe the interactive effects of CDDP and AgSD. AgSD pretreatment significantly decreased the concentrations of platinum in blood and in kidney tissue compared to the control. AgSD also diminished the CDDP-induced abnormalities of serum creatinine level but did not affect CTR1 expression. In contrast, no significant change was observed in platinum concentration in liver tissue after AgSD pretreatment. However, the level of alanine aminotransferase increased after administration of CDDP with or without AgSD. These results suggest that CDDP administered intravenously interacts with AgSD applied to region of wound, in association with changing the platinum concentrations in blood and tissue distribution. The interactive effects of CDDP may relate to modulate the function of platinum transferring via CTR1 in the presence of Ag.

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