A method for continuous drug infusion in unrestrained rats: its application in evaluating the toxicity of 5-fluorouracil/thymidine combinations.

A method for continuous infusion of drugs into the tail vein of rats was developed. This simple procedure has the advantage of permitting freedom of movement of the animal during extended drug exposure. Utilization of an aluminum sheath as a tail cover prevents destruction of the cannulating apparatus without placing additional stress upon the animal. This method produced no adverse effects upon rats during prolonged infusion (up to 7 days) and may be useful in the routine evaluation of agents having a short plasma half-life. The lethality of FU alone or in combination with TdR was evaluated with this technique. Infusion of up to 10 gm/kg/72 hr of TdR produced no mortality. Co-administration of TdR at 1 gm/kg/72 hr with FU, however, potentiated the toxicity of FU. These data indicate that the toxicity of FU may be modified by provision of TdR with this method.