[Drug interactions between interferon alpha 2b and 5-fluorouracil during continuous intravenous 5FU infusion]

The concentration-time profile of 5-fluorouracil (5FU) in serum of patients during continuous infusion of 5FU for five days was investigated. The coadministration of each of 5 million units interferon-alpha-2b (IFN) on day 2 and 4 of the infusion causes an accumulation of 5FU in the serum at about 120% on day 3 in compare to the control (day 1 of infusion without IFN). On day 5 of the infusion the mean 5FU serum concentrations are about 170% higher than on day 1 with a level of probability ranging from p < 0.0003 to p < 0.043. Mean AUC-values increase from 5454 ng/ml.h (day 1) to 12069 ng/ml.h (day 3, p < 0.05) and subsequently to 14919 ng/ml.h on day 5 (p < 0.005). IFN causes an decrease of the total body clearance from 2949 ml/h (day 1) to 1959 ml/h on day 3 and to 1258 ml/h on day 5 (p < 0.008), respectively. There might exist a linear correlation between the order of magnitude of the 5FU serum concentrations and its pharmacokinetic parameters on day 1, 3 and 5 and the administration of IFN, because a close correlation ranging from R = 0.972 to R = 0.999 have been found in regression analysis.