5-FU uptake in liver metastases after intravenous and intraperitoneal administration: an autoradiographic study in the rat.
OBJECTIVE
To analyse 5-fluorouracil (5-FU) uptake in hepatic metastases and normal tissues after intravenous (i.v.), intraperitoneal (i.p.e.) and intraportal (IPO) administration.


RESULTS
A total of 18 inbred rats with hepatic metastases were injected with 14C-labelled 5-FU either through the i.v. (n = 7), i.p.e (n = 7) or IPO (n = 4) route. Radioactivity was visualised autoradiographically and quantified by computer-based image analysis. After 20 minutes, 10 i.v. injected tumours showed a higher amount of radioactivity (mean +/- SD) 23.8 +/- 7.8 than 6 i.p.e. injected (16.5 +/- 5.1, P = 0.06). At 2 hours, 9 i.v. injected metastases contained more radioactivity (49.6 +/- 9.2) than 19 i.p.e. injected tumours (28.2 + 11.3, P = 0.00003). After 24 hours, 2 i.p.e. injected tumours had higher radioactivity (mean 25.2) compared with 7 i.v. injected (7.6 +/- 4.1). IPO administration did not confer higher radioactivity at any time point. When the calculations were based on average metastatic radioactivity of individual rats, the difference between i.v. and i.p.e. injected rats was still present at 2 hours.


CONCLUSIONS
These results indicate that early tumour 5-FU uptake after intraperitoneal and intraportal administration may be inferior to that after intravenous injection. Deposition of the drug in the peritoneal cavity may, however, act as a slow release preparation giving continuous drug exposure for prolonged periods of time. These results suggest a role for combined intravenous and intraperitoneal adjuvant therapy.
Mahteme
H
H
Department of Surgery, Uppsala University, Sweden.
Larsson
B S
BS
Sundin
A
A
Graf
W
W
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics*; D001345:Autoradiography; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary*; D051381:Rats; D017208:Rats, Wistar
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil