Effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine on life-span and 5-fluorouracil metabolism in mice with hepatic metastases.
5-Fluorouracil (5FU) is rapidly metabolised in the liver by dihydrouracil dehydrogenase. Bromovinyluracil is formed in the liver from (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) by pyrimidine nucleoside phosphorylase and is a potent inhibitor of dihydrouracil dehydrogenase. The co-administration of 5FU (intravenously) and BVDU (orally) was investigated in normal BDF1 mice and in those bearing liver metastases of Lewis lung carcinoma. 5FU alone rapidly disappeared from plasma and liver within 60 min of dosing. Administered with BVDU, 5FU persisted in plasma and liver for 60-180 min. The combination also significantly enhanced the life-span of tumour-bearing mice. 5FU plus BVDU may have therapeutic potential in the treatment of primary and secondary liver tumours.
Iigo
M
M
Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan.
Nishikata
K
K
Nakajima
Y
Y
Hoshi
A
A
De Clercq
E
E
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000998:Antiviral Agents / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005472:Fluorouracil / Q000378:metabolism*; D008017:Life Expectancy; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D008815:Mice, Inbred Strains
D000998:Antiviral Agents; C020235:brivudine; D001973:Bromodeoxyuridine; D005472:Fluorouracil