[Experimental studies on the optimal therapeutic mode of intra-arterial infusion of 5-fluorouracil. (2) Concentrations within the tumors and normal tissues and therapeutic and adverse effects of 5-fluorouracil delivered by various routes].
5-Fluorouracil levels in Yoshida sarcoma implanted subcutaneously and some organs of rats were measured following intraarterial or intravenous administration of 5-FU at various infusion time and doses, and the relationship between 5-FU level in tumors and antitumor effect was examined. The antitumor effect following intraarterial infusion of 5-FU was superior to its systemic administration. With intraarterial infusion, higher levels of 5-FU in tumors could be expected during infusion and immediately after injection. One-shot intraarterial injection of 5-FU was much more effective than continuous infusion of 5-FU from view points of the antitumor effect. This reason might be attributed to that, 5-FU level in the tumor after one shot intraarterial injection was maintained higher for many longer period than its level during continuous infusion. 5-FU levels in the liver following and during intraaortic infusion of 5-FU showed interesting change, i.e. if 5-FU levels flowing into the liver was low, 5-FU in the liver was not detected at all, however, if high level of 5-FU was flown into, the liver 5-FU was measured even 24 hours after injection. It was supposed that the low level of 5-FU was degraded by the liver easily, but the high level of 5-FU flown into the liver could not be metabolized. From these experiments it may be concluded that infusion time of intraarterial administration of 5-FU must be as short as possible within tolerable toxicity, and infusion doses must be as high as possible that could be degraded by the liver for reduction of toxicity.
D000818:Animals; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000032:analysis; D007261:Infusions, Intra-Arterial / Q000379:methods; D051381:Rats; D012517:Sarcoma, Yoshida / Q000032:analysis / Q000188:drug therapy*; D014018:Tissue Distribution
D005472:Fluorouracil