Suppository delivery of 5-fluorouracil in rectal cancer.
BACKGROUND
Preoperative radiotherapy with concomitant intravenous 5-fluorouracil (5-FU-i.v.) is effective in shrinking locally advanced rectal cancers and facilitating subsequent surgery. Topical 5-FU application may enhance its radiosensitizing and cytotoxic effects. Suppository and intravenous 5-FU administration were compared with respect to myelo-suppression and tissue concentrations.


METHODS
Rats received 120 mg/kg 5-FU-i.v. or via suppository (5-FU-S). White blood cell count, serum albumin, alkaline phosphatase, creatinine, and aspartate aminotransferase (AST) were determined before and serially after 5-FU administration. In a separate experiment, rats received 5-FU-S or 5-FU-i.v. as already described. Portal and systemic blood, rectal, iliac lymph node, liver, and lung tissue were harvested for high-performance liquid chromatography determination of 5-FU concentrations 30 min, 1, 3, 6, and 12 h after drug administration.


RESULTS
No toxicity was observed in 5-FU-S animals, whereas 63% of 5-FU-IV animals had diarrhea. Weight loss and myelosuppression occurred only in 5-FU-i.v. animals. Rectal drug concentrations were significantly higher in the 5-FU-S animals compared with 5-FU-i.v. animals, 0.5-6 h after drug administration. Blood, liver, and lung 5-FU concentrations with 5-FU-S were comparable to those with 5-FU-i.v.


CONCLUSIONS
5-FU suppositories are associated with fewer systemic side effects and higher rectal 5-FU concentrations than with 5-FU-i.v. administration.
Galandiuk
S
S
Department of Surgery, University of Louisville, Kentucky 40292, USA.
Wrightson
W
W
Marr
L
L
Myers
S
S
LaRocca
R V
RV
D000285:Administration, Rectal; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D003967:Diarrhea / Q000139:chemically induced; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012004:Rectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D012007:Rectum / Q000378:metabolism; D013488:Suppositories; D014018:Tissue Distribution; D015431:Weight Loss / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D013488:Suppositories; D005472:Fluorouracil