Modulation of the effects of fluoropyrimidines on toxicity and tumor inhibition in rodents by uridine and thymidine.

Uridine and/or thymidine were administered concomitantly with 5-fluorouracil (5-FU) and 5'-deoxy-5-fluorouridine (5'-dFUR) to mice and rats in order to establish whether the physiological nucleosides acting in vitro as antagonists can diminish fluoropyrimidine toxicity in vivo. In addition, the influence of orally co-administered uridine on antitumor activity of 5-FU and 5'-dFUR in mice has been studied. All co-administrations aggravated the general toxicity of both fluoropyrimidines. Tumor inhibition was enhanced by uridine, but the therapeutic ratio was not improved compared to monotherapy with either 5-FU or 5'-dFUR.