{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T07:41:20Z","timestamp":1697096480109},"reference-count":17,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2010,12,28]],"date-time":"2010-12-28T00:00:00Z","timestamp":1293494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2011,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In the case of cancer chemotherapy for hepatocellular carcinoma, 5\u2010fluorouracil (5\u2010FU) is used widely, and has typically been given by intrahepatic arterial (i.a.) infusion to increase treatment efficacy and to reduce systemic toxicity. 5\u2010Fluorouracil is eliminated primarily by the liver, and so its use in patients with hepatic disease can be difficult. This study investigated the effect of hepatic fibrosis on the pharmacokinetics of 5\u2010FU in rats. Experimental hepatic fibrosis was induced by carbon tetrachloride treatment. 5\u2010Fluorouracil was infused for 15\u2009min into the hepatic artery or the saphenous vein of the rats at a dose of 1.25\u2009mg\/kg. There were no significant differences in the plasma concentration and <jats:italic>AUC<\/jats:italic> of 5\u2010FU between hepatic disease rats and their controls after both intravenous and intraarterial injection. This result is probably attributed to the fact that there were no significant differences in hepatic blood flow and dihydropyrimidine dehydrogenase (DPD; an initial and rate\u2010limiting enzyme in 5\u2010FU catabolism) activity between hepatic disease rats and their controls, because the total clearance of 5\u2010FU after intravenous and intraarterial administration is mainly limited by hepatic blood flow and DPD activity, respectively. In conclusion, the pharmacokinetics of 5\u2010FU is not affected by hepatic fibrosis, unlike that of many hepatically metabolized drugs. 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