Effect of acute hepatic failure on the hepatic first-pass effect of 5-fluorouracil in rats.
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.
Nagata
Masashi
M
Department of Pharmacy, University of Miyazaki Hospital, Kiyotake-cho, Miyazaki.
Hidaka
Yumi
Y
Hidaka
Muneaki
M
Kawano
Yohei
Y
Iwakiri
Tomomi
T
Okumura
Manabu
M
Arimori
Kazuhiko
K
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
D000970:Antineoplastic Agents; D005472:Fluorouracil