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

摘要: Abstract We have attempted to evaluate the degree which hepatic arterial infusion of 5-fluoro-2′-deoxyuridine (FdUrd) or 5-fluorouracil produces higher and lower systemic drug concentrations than are achieved with corresponding peripheral venous infusions. Hepatic catheters were placed for therapy in 15 patients primary metastatic liver cancer. Temporary allowed direct sampling levels effluent as well measurement blood flow. FdUrd was measured primarily by radioimmunoassay fluorouracil a high-pressure liquid chromatographic system. Due limited sensitivities these assays, short (40 60 min) infusions at dose rates 10 100 times those conventionally used given order produce that could be reliably. Even 0.5 40 mg/kg body weight/hr 5.6 fluorouracil, steady state bloodstream 30 min extraction quantified. The is high an ratio (hepatic level — level/hepatic level) 0.69 0.92 clearance 0.81 2.3 liters/min. however, appears 0.22 0.45 0.24 With infusion, 94 99% 19 51% extracted one pass. levels, measure intrahepatic concentration tumor capillary bed, 4-fold 1.5-fold when route. Systemic only about 25% infusion. also 60% These results support means improve therapeutic index treatment cancer liver. Although molar equivalent this study, differences pharmacology noted above may not applicable conventional where much used. Nonetheless, type analytical approach should prove valuable evaluation other agents chemotherapy.