Recombinant human interferon alpha-2a increases the antitumor activity of 5-fluorouracil on human colon carcinoma xenograft Co-4 without any change in 5-FU pharmacokinetics.

We investigated the modulating effect of recombinant human interferon alpha-2a (IFN-alpha) on the antitumor activity of 5-fluorouracil (5-FU) against a human colon carcinoma xenograft (Co-4) in nude mice with reference to changes in the pharmacokinetic pattern of 5-FU. Mice bearing Co-4 received 5-FU ip at a dose of 90 mg/kg once with or without IFN-alpha, which was administered sc at a dose of 60.000 IU/mouse daily for 7 days before 5-FU treatment. When the area under the curve (AUC) and peak plasma concentration (Cmax) of 5-FU with or without IFN-alpha were measured as pharmacokinetic parameters, the pharmacokinetics of 5-FU was not changed by IFN-alpha administration. This result suggests that the modulating effect of IFN-alpha on 5-FU does not involve augmentation of 5-FU pharmacokinetic parameters.