INFLUENCE OF DIFFERENT DOSES OF INTERFERON-ALPHA-2B ON THE BLOOD-PLASMA LEVELS OF 5-FLUOROURACIL

The blood plasma levels of 5-fluorouracil (5FU) after i.v. administration have been determined without and under the influence of 1, 5 or 9 million units (MU) preadministered interferon (IFN) in patients with gastrointestinal carcinoma. The co-administration of 9 MU IFN causes a doubled increase of the 5FU serum concentrations combined with a statistically significant change of the pharmacokinetics of 5FU for c(0), AUC, Vd and Cl-tot (P < 0.005). A similar effect with distinctly increased serum concentrations could be observed for the preadministration of 5 mU IFN whereby c(0) and AUC were elevated significantly (P < 0.05), but not Vd, CL(tot) and cd. The preadministration of 1 MU IFN also leads to higher plasma levels, but no changes in the pharmacokinetics of 5FU could be calculated (P > 0.05). A linear correlation between the IFN dose and the pharmacokinetic parameters c(0) (R = 0.958), AUC(0-120) (R = 0.948), Vd (R = 0.941) and Cl-tot (R = 0.963) of 5FU could be found (P < 0.05), but not for the coefficient of distribution and t(1/2)el. The results indicate that the pharmacokinetics of 5FU might be influenced by the preadministered IFN dose.