Pharmacokinetics of 1-alkylcarbamoyl-5-fluorouracils in plasma and ascites fluid after oral administration in mice.
Pharmacokinetics of 1-alkylcarbamoyl-5-fluorouracils was examined in mice bearing sarcoma 180. The alkylcarbamoyl derivatives were absorbed rapidly as intact form through the gastrointestinal tract and distributed into ascites fluid. Concentration-x-time (C-x-t) values of 5-fluorouracil formed in plasma and ascites fluid decreased in order by extension of the carbon chain of the alkyl moiety. C-x-t value of 5-fluorouracil formed in ascites fluid after hexylcarbamoyl derivative was higher than that in plasma. Antitumor activity of the compounds was correlated with both maximum concentration (Cmax) and C-x-t values of 5-fluorouracil formed and Cmax of total (intact form plus 5-fluorouracil formed) in ascites fluid (P < 0.01), and with C-x-t values in ascites fluid and Cmax and C-x-t values of 5-fluorouracil formed in plasma (P < 0.05). Alkylcarbamoyl structure was valuable for rapid absorption through the gastrointestinal tract and blood-ascites barrier and for maintenance of 5-fluorouracil level in plasma and ascites fluid.
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D001202:Ascitic Fluid / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D012510:Sarcoma 180 / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013997:Time Factors
D000970:Antineoplastic Agents; D005472:Fluorouracil