Pharmacokinetics of 5-fluorouracil following different routes of intrahepatic administration in the canine model. Cancer Res 1984 Nov;44(11):5105-9
Date
11/01/1984Pubmed ID
6488170Scopus ID
2-s2.0-0021690651 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
In an effort to achieve high concentrations of 5-fluorouracil (5-FUra) in the hepatic circulation while minimizing systemic exposure, several routes of intrahepatic administration were compared in the canine model. To ascertain these data, 5-FUra (30 mg/kg) was given as a bolus into either a systemic vein (femoral vein), hepatic artery, hepatic artery distal to its ligation after hepatic dearterialization, or through the portal vein. Three dogs were studied for each route with concomitant blood samples taken from the inferior vena cava and hepatic vein at 1, 2, 3, 5, 10, 15, 30, and 60 min after injection. 5-FUra levels were determined in plasma by high-pressure liquid chromatography. Blood flow in the portal vein and hepatic artery was measured by an electromagnetic flowmeter. The data were best described by a multicompartmental model including the measured flows. Hepatic components of the model were separate arterial and portal compartments, with elimination from each described by linear kinetics. Analysis of the results indicated that the highest hepatic levels with the least systemic exposure, as indicated by drug levels in hepatic and peripheral vein, were realized following hepatic artery administration distal to its ligation after hepatic dearterialization.
Author List
Didolkar MS, Covell DG, Jackson AJ, Walker AP, Kalidindi SRMESH terms used to index this publication - Major topics in bold
AnimalsDogs
Femoral Vein
Fluorouracil
Hepatic Artery
Hepatic Veins
Injections, Intra-Arterial
Injections, Intravenous
Liver
Portal Vein
