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• W2047197490 abstract "Purpose—Amifostine is a prodrug in which selectivity is largely determined by the preferential formation and uptake of its cytoprotective metabolite, WR-1065, in normal tissues as a result of differences in membrane-bound alkaline phosphatase activity. It was hypothesized that amifostine may be a good candidate for regional drug delivery to the liver because of its large hepatic extraction and total body clearance. Methods—Rat livers were implanted with Walker-256 tumors. The tumor-bearing rats received 15 min infusions of amifostine (200 mg/kg) via the portal vein or the femoral vein. WR-1065 concentrations in the blood, liver and tumor were measured at various times. Results—The WR-1065 tumor portal dosing AUC15−60 was 40% of systemic dosing, and tumor concentrations following portal dosing were one-fifth of that following systemic dosing. The portal dosing WR-1065 liver AUC15−60 was 60% higher than the values for systemic dosing. The liver/tumor concentration ratios of WR-1065 following portal dosing were up to 8-fold higher than the ratio following systemic administration. Unfortunately, systemic exposure to WR-1065 was greater following portal vs systemic amifostine. Conclusions—Amifostine may provide increased liver protection and decreased tumor protection from radio- or chemotherapy when administered by the portal vein. However, portal dosing also increases systemic exposure to WR-1065, which is associated with hypotension. Copyright © 2004 John Wiley & Sons, Ltd." @default.
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• W2047197490 date "2004-01-01" @default.
• W2047197490 modified "2023-10-16" @default.
• W2047197490 title "Disposition of WR-1065 in the liver of tumor-bearing rats following regional vs systemic administration of amifostine" @default.
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• W2047197490 doi "https://doi.org/10.1002/bdd.380" @default.
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