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 reference to changes in the pharmacokinetic pattern of 5-FU. Mice bearing Co-4 received 5-FU ip at a dose of 90 mg/kg once with or without IFN-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 augmentation of 5-FU pharmacokinetic parameters.
Kase
S
S
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Kubota
T
T
Watanabe
M
M
Furukawa
T
T
Tanino
H
H
Kuo
T H
TH
Saikawa
Y
Y
Teramoto
T
T
Kitajima
M
M
D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D005472:Fluorouracil / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D011994:Recombinant Proteins; D014183:Transplantation, Heterologous
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D005472:Fluorouracil