Biologic activity of 5'-deoxy-5-fluorouridine by rectal administration.
5'-Deoxy-5-fluorouridine (dFUR) is used orally to treat human malignancies. This study compared the antitumor activity and toxicity of rectally and orally administered dFUR. A 7-day treatment of dFUR (350 or 700 mg/kg/day) was infused rectally over 30 min or administered by oral gavage (500 mg/kg/day) to rats bearing transplanted dimethylhydrazine-induced colon tumors. The oral treatment was previously shown to produce a 82% cure of the tumor-bearing animals. The tumor weight after 7 day treatment was compared to that before treatment. The size of the tumor in the saline-treated control group (N = 6) increased by 55%. The maximum tumor size reductions by drug treatments were 40% for the 350-mg/kg rectal dose (N = 5), greater than 99% for the 700-mg/kg rectal dose (N = 10), and 100% for the 500-mg/kg oral dose (N = 4). The 350-mg/kg rectal dose did not produce any cures, while the 700-mg/kg rectal dose produced 80% cures and the 500-mg/kg oral dose 100% cures. The cured animals remained tumor-free during the observation period of 163 to 243 days. The tumor-bearing rats were euthanized between 46 and 132 days when they appeared moribund or when the tumor began to ulcerate. The 700-mg/kg rectal and 500-mg/kg oral treatments produced greater weight loss than saline suggesting a drug-induced intestinal toxicity. After rectal drug treatment, the animal weight returned to pretreatment level within 3 days, indicating a rapidly reversible intestinal toxicity. The oral group suffered a greater weight loss than the rectal group and took more than 10 days to recover.2+his suggests that the intestinal
Bramer
S L
SL
College of Pharmacy, Ohio State University, Columbus 43210.
Gunnarsson
L C
LC
Au
J L
JL
D000285:Administration, Rectal; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007958:Leukocyte Count; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010976:Platelet Count; D051381:Rats
D000970:Antineoplastic Agents; D005467:Floxuridine; C025034:doxifluridine