Clinical pharmacokinetics of 5-fluorouracil. Influence of the biomodulating agents interferon, dipyridamole and folinic acid alone and in combination.

The pharmacokinetics of the antimetabolite 5-fluorouracil (5FU, CAS 51-21-8) were investigated under the influence of the biomodulating agents folinic acid (FA), FA combined with dipyridamole (DPM), DPM, interferon-alpha-2b (IFN), and IFN combined with DPM. IFN as well as IFN/DPM cause an enormous increase of the 5FU plasma concentrations resulting in a statistically significant change of the pharmacokinetics. The mean initial plasma concentrations of 5FU are increased at about 143% under the influence of IFN and at 162% under the influence of IFN/DPM. Accordingly, the mean area under the concentration-time curve is elevated at 114% for IFN and at 184% for IFN/DPM. The volume of distribution (IFN - 39%, IFN/DPM - 38%) as well as the total body clearance (IFN - 30%, IFN/IFN - 44%) are lowered distinctly. In contrary, the coadministration of either FA or DPM or FA/DPM to 5FU does not lead to a significant change in the pharmacokinetic profile of 5FU, but also causes higher plasma concentrations. The present results indicate that the coadministration of biomodulators can lead to distinct changes of the 5FU kinetics, but must not be useful in each case.