Regional Pharmacokinetics of 5-Bromo-2′-deoxyuridine and 5-Fluorouracil in Dogs: Hepatic Arterial versus Portal Venous Infusions

摘要: Abstract The purpose of this study was to determine the effect route hepatic administration drug on regional pharmacokinetics and systemic exposure 5-fluorouracil (FUra) 5-bromo-2′-deoxyuridine (BrdUrd). A total 13 mixed-breed male female dogs were used in these acute studies. Each dog administered arterial portal venous infusions a single drug, cross-over fashion, at two dose rates for four sequential infusions. BrdUrd studied 0.250 0.500 µmol/min/kg, FUra 0.125 µmol/min/kg. infusion lasted 2 h, which time steady-state plasma concentrations obtained ( i.e. , gastroduodenal artery, vein, femoral artery), perfusion artery vein measured, extraction (as opposed across splanchnic region) directly assessed. found be highly extracted liver E H ≥ 0.65) studied, resulting low values fraction escaping presystemic elimination F ≤ 0.35). In addition, kinetics extraction, first-pass liver, clearance) C FA ) not significantly different following versus drug. Thus, it appears that chemotherapy may applied halogenated pyrimidines arterial, venous, alternating dosing routes with no additional risk toxicity.