title: Effect of acute hepatic failure on the hepatic first-pass effect of 5-fluorouracil in rats.
abstract: OBJECTIVE
  In cancer chemotherapy for hepatocellular carcinoma, 5-fluorouracil is widely used and has typically been given by intrahepatic arterial (i.a.) infusion to increase treatment efficacy and reduce systemic toxicity. 5-Fluorouracil is eliminated primarily by the liver and so the hepatic first-pass effect after intrahepatic arterial administration of 5-fluorouracil may be lower in patients with hepatic failure, and systemic toxicity may not be reduced. In this study, we have investigated the effect of acute hepatic failure on the first-pass effect of 5-fluorouracil in rats.
  
  
  METHODS
  Experimental acute hepatic failure was induced by treatment with carbon tetrachloride (CCl4). 5-Fluorouracil was infused for 15 min into the hepatic artery or the saphenous vein of rats at a dose of 1.25 mg/kg.
  
  
  RESULTS
  Hepatic availability in 50% CCl4-treated (severe hepatic failure) rats was higher than in controls.
  
  
  CONCLUSIONS
  The hepatic first-pass effect after intrahepatic arterial administration of 5-fluorouracil was lower in severe hepatic failure. Therefore, the reducing effect of the systemic toxicity after intrahepatic arterial administration may be lower in severe hepatic failure.
authors.affiliation: Department of Pharmacy, University of Miyazaki Hospital, Kiyotake-cho, Miyazaki.
authors.forename: Masashi
authors.initials: M
authors.lastname: Nagata
authors.forename: Yumi
authors.initials: Y
authors.lastname: Hidaka
authors.forename: Muneaki
authors.initials: M
authors.lastname: Hidaka
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kawano
authors.forename: Tomomi
authors.initials: T
authors.lastname: Iwakiri
authors.forename: Manabu
authors.initials: M
authors.lastname: Okumura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Arimori
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002252:Carbon Tetrachloride Poisoning / Q000150:complications / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000150:complications / Q000378:metabolism*; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008658:Inactivation, Metabolic; D007262:Infusions, Intravenous; D008099:Liver / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D005472:Fluorouracil