Pharmacokinetic interaction of 5-fluorouracil and interferon alpha-2b with or without folinic acid.
The purpose of this study was to evaluate a potential pharmacokinetic (PK) interaction between fluorouracil (5-FU) and the biomodulating agent interferon alpha (IFN-alpha) in patients with metastatic colorectal carcinoma. 5-FU was applied as an intravenous bolus injection of 750 mg m-2 weekly and IFN-alpha 2b (IFN) 5 MU was injected 3 times weekly (TIW) subcutaneously. In the first study, 13 patients were treated by this schedule, 5-FU plasma levels were determined by HPLC on day (d) one as baseline before starting IFN; the analysis was repeated at the second or third cycle of 5-FU administration 1 hour after the last IFN injection respectively. In the second study, 10 patients additionally received folinic acid (FA) 200 mg m-2 as a short time infusion immediately before 5-FU, and a third analysis of FU kinetics was performed in order to compare the influence of a double modulation of IFN and FA to IFN alone. Combination of 5-FU and IFN resulted in a significant increase of the AUC of 5-FU (80%) and the fictive initial concentration (C0, 65%) obviously caused by a reduction of 5-FU clearance by 50%. However, when FA was added to this schedule, no significant changes of FU kinetics compared to 5-FU alone could be documented. Finally, in two pilot patients 5-FU 750 mg was given as a continuous infusion (CI) over 5 days and IFN 5 x 10(6) u was added daily from d2 to d5.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Oncology, Hospital Rudolfstiftung, Vienna, Austria.
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Czejka
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002955:Leucovorin / Q000008:administration & dosage* / Q000494:pharmacology; D011994:Recombinant Proteins
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002955:Leucovorin; D005472:Fluorouracil