[Study on the pharmacokinetics of UFT in patients with hepatocellular carcinoma associated with cirrhosis].
UFT was administered preoperatively in 20 cases of primary hepatocellular carcinoma, and tegafur, 5-fluorouracil (5-FU), uracil, total thymidylate synthase (TS) and free TS in blood and liver tissue were determined. The results were as follows. 1. Tegafur level was significantly high in blood, while the levels of 5-FU and uracil were high in the liver tissue. The 5-FU level in the cancerous area was 0.099 micrograms/g, higher than the effective level regardless of the presence or not of complication with liver cirrhosis. 2. Total TS, FdUMP (computed as total TS-free TS) and TS inhibition rate [(computed as (TS-free TS)/TS x 100 (%)] were significantly higher in the cancerous liver tissue than in the non-cancerous area. In the cases where determination was made simultaneously for the cancerous liver and non-cancerous liver tissues, the FdUMP level and TS inhibition rate in the cancerous liver tissue were high in 14 out of 17 cases (82.4%) and 13 out of 17 cases (76.5%) respectively. Therefore, UFT seems to have selective toxicity. 3. No correlation was found between 5-FU level, total TS, FdUMP in the liver tissue on the one hand and TS inhibition rate on the other. 4. UFT yielded sufficient 5-FU levels in the cancerous area regardless of the presence or not of complication with cirrhosis and therefore is expected to inhibit DNA synthesis selectively in the cancerous tissue.
Une
Y
Y
1st Dept. of Surgery, Hokkaido University School of Medicine.
Ito
Y
Y
Ogasawara
K
K
Nagafuchi
E
E
Matsuoka
S
S
Misawa
K
K
Sato
N
N
Nakajima
Y
Y
Uchino
J
J
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics*; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000032:analysis / Q000097:blood; D006801:Humans; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000150:complications / Q000378:metabolism*; D008113:Liver Neoplasms / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D005641:Tegafur / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D013940:Thymidylate Synthase / Q000032:analysis / Q000097:blood; D014498:Uracil / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics
D005641:Tegafur; D014498:Uracil; D013940:Thymidylate Synthase; D005472:Fluorouracil