Journal article
Role of administration route in the therapeutic efficacy of doxifluridine
JNCI : Journal of the National Cancer Institute, Vol.78(3), pp.527-532
1987
DOI: 10.1093/jnci/78.3.527
PMID: 2950266
Abstract
Effect of drug administration route on the therapeutic efficacy of the 5-fluorouracil (FUra) analogue doxifluridine [(5′-dFUrd); 5′-deoxy-5-fluorouridine] was investigated in Fischer CDF rats bearing a chemically induced transplantable colon carcinoma sensitive to fluoropyrimidines. The antitumor activities of 5′-dFUrd and of its parent drug FUra were evaluated after 7 days of continuous administration (by iv infusion, iv push, or po route) of doses ranging from 125 to 750 mg 5′-dFUrd/kg/day and from 12.5 to 55 mg FUra/kg/day. At the maximally tolerated dose, 5′-dFUrd (500 mg/kg/day) and FUra (25–35 mg/kd/day) were equally effective in producing cures when treatments were performed by either continuous iv infusion or iv push. 5′-dFUrd was more effective than FUra when these agents were administered orally (82% cures for 5′-dFUrd vs. 30% cures for FUra). Concentrations of 5′-dFUrd and its metabolite FUra in the blood and urine of normal and tumor-bearing rats were determined by high-performance liquid chromatography following administration of 500 mg 5′-dFUrd/kg. Pharmacokinetic studies indicated that at comparable antitumor activity, systemic exposures to FUra derived from 500 mg 5′-dFUrd/kg administered by iv push, orally, or continuous iv infusion were 3.5±1.0, 3.2±1.1, and 1.5±0.3 mM·min, respectively. Antitumor activity and pharmacokinetic results obtained in this model system indicated that 1) 5′-dFUrd is an active agent that can produce cures regardless of the route of administration employed and 2) among the three methods of drug administration tested, comparable tumor-free survival can be achieved by continuous iv infusion of 5′-dFUrd with the concomitant lowest systemic exposure to the cytotoxic metabolite FUra.
Details
- Title: Subtitle
- Role of administration route in the therapeutic efficacy of doxifluridine
- Creators
- Fabio Trave - Roswell Park memorial inst., grace cancer drug cent., Buffalo NY 14263, United StatesLuciano Canobbio - Roswell Park memorial inst., grace cancer drug cent., Buffalo NY 14263, United StatesJ. Lai-Sim Au - Grace (United States)Youcef M Rustum - Grace (United States)
- Resource Type
- Journal article
- Publication Details
- JNCI : Journal of the National Cancer Institute, Vol.78(3), pp.527-532
- DOI
- 10.1093/jnci/78.3.527
- PMID
- 2950266
- NLM abbreviation
- J Natl Cancer Inst
- ISSN
- 0027-8874
- eISSN
- 1460-2105
- Publisher
- Oxford University Press
- Language
- English
- Date published
- 1987
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359849302771
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