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 r eference to changes in the pharmacokinetic pattern of 5-FU. Mice beari ng Co-4 received 5-FU ip at a dose of 90 mg/kg once with or without IF N-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 augm entation of 5-FU pharmacokinetic parameters.