A clinical-pharmacological evaluation of hepatic arterial infusions of 5-fluoro-2'-deoxyuridine and 5-fluorouracil.

作者：William D. Ensminger, André Rosowsky, Vic Raso, David C. Levin, Michael Glodé, Steven E. Come, Glenn D. Steele, Emil Frei · 发表于：PubMed · 年份：1978 · 被引用次数：521 · 研究领域：Colorectal Cancer Treatments and Studies、Pancreatic and Hepatic Oncology Research、Cancer Treatment and Pharmacology

Abstract We have attempted to evaluate the degree to which hepatic arterial infusion of 5-fluoro-2′-deoxyuridine (FdUrd) or 5-fluorouracil produces higher hepatic and lower systemic drug concentrations than are achieved with corresponding peripheral venous infusions. Hepatic arterial catheters were placed for therapy in 15 patients with primary or metastatic liver cancer. Temporary hepatic venous catheters allowed direct sampling of drug levels in the hepatic venous effluent as well as measurement of hepatic blood flow. FdUrd was measured primarily by radioimmunoassay and fluorouracil by a high-pressure liquid chromatographic system. Due to the limited sensitivities of these assays, short (40 to 60 min) infusions at dose rates 10 to 100 times those conventionally used were given in order to produce drug levels that could be measured reliably. Even at dose rates of 0.5 to 40 mg/kg of body weight/hr for FdUrd and 5.6 mg/kg of body weight/hr for fluorouracil, steady state drug levels were achieved in the bloodstream in 30 to 40 min and hepatic extraction could be quantified. The hepatic extraction of FdUrd is high with an extraction ratio (hepatic arterial level — hepatic venous level/hepatic arterial level) of 0.69 to 0.92 and a clearance of 0.81 to 2.3 liters/min. The hepatic extraction of fluorouracil, however, appears to be lower with an extraction ratio of 0.22 to 0.45 and a clearance of 0.24 to 0.45 liters/min. With hepatic arterial drug infusion, 94 to 99% of FdUrd and 19...