Influence of different doses of interferon-α-2b on the blood plasma levels of 5-fluorouracil

Abstract

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 c0, AUC, Vd and Cltot (P < 0.005). A similar effect with distinctly increased serum concentrations could be observed for the preadministration of 5 mU IFN whereby c0 and AUC were elevated significantly (P < 0.05), but not Vd, Cltot 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 c0 (R = 0.958), AUC0-120 (R = 0.948), Vd (R = 0.941) and Cltot (R = 0.963) of 5FU could be found (P < 0.05), but not for the coefficient of distribution and t1/2el. The results indicate that the pharmacokinetics of 5FU might be influenced by the preadministered IFN dose.

5-fluorouracil and low-dose recombinant interferon-α-2a in patients with hormone-refractory adenocarcinoma of the prostate

“…This study demonstrated that a regimen which consisted of 5-FU (750 mg/m 2 ; continuous infusion on D1-D5, followed by bolus injection on D12 and D19) and IFN-␣ (3 million IU on D1-D5, followed by 5 million IU on D11-D13 and D18-D20) might be more effective than one consisting of 5-FU (750 mg/ m 2 ; continuous infusion on D1-D5, followed by weekly bolus injection) and IFN-␣ (5 million IU on D1, D3, and D5, followed by 9 million IU given weekly), suggesting that a higher dose of IFN-␣ does not always bring about a higher objective response rate in a clinical setting. Moreover, Czejka et al [20] reported that there is no significant difference in pharmacokinetics of 5-FU between two doses of preadministered IFN-␣ (5 million IU and 9 million IU). These results suggest that, in the biochemical modulation of 5-FU by IFN-␣, administration of a higher dose (9 million IU) of IFN-␣, which was used in a previous report, does not necessarily enhance the cytotoxic effects of 5-FU against hormone-refractory prostate cancer.…”

Disposition of 5-formyl- and 5-methyltetrahydrofolic acid in serum after i.v. bolus of calcium folinate: pharmacokinetic drug interaction with preadministered interferon-alpha-2b

“…Analysis of serum and red blood cell samples revealed that the biotransformation of CHO-THFA into CH3-THFA also takes place in red blood cells (a subcompartment of the blood) within a few minutes after administration of folinic acid (15)(16)(17)(18)(19).…”