Abstract
As part of a Phase I clinical trial, 5 patients received 5-fluorouracil (FU) both singly and in combination with misonidazole (MISO) for the treatment of gastrointestinal cancer. Concentrations of total FU and F-containing metabolites in urine specimens, taken during 48 h after therapy, were determined. The clearance of FU following administration of 1.0 or 1.5 g FU m2 was significantly reduced by treatment with MISO (1.75-2.0 gm-2) given 2 h prior to FU therapy. Reduced clearance of FU by MISO was associated with an earlier onset of the period of nonlinearity of FU pharmacokinetics and an increased half-life of elimination. Furthermore, the clearance of FU correlated inversely with the severity of gastrointestinal toxicity. The mechanism of MISO enhancement of FU action is unlikely to be competition for microsomal enzymes, as proposed for the interaction of MISO and alkylating agents, since FU is catabolized at mitochondrial and cytosolic sites.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 24 print issues and online access
$259.00 per year
only $10.79 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Rights and permissions
About this article
Cite this article
McDermott, B., Van den Berg, H., Martin, W. et al. Pharmacokinetic rationale for the interaction of 5-fluorouracil and misonidazole in humans. Br J Cancer 48, 705–710 (1983). https://doi.org/10.1038/bjc.1983.253
Issue Date:
DOI: https://doi.org/10.1038/bjc.1983.253
This article is cited by
-
Clinical Management of Cytotoxic Drug Overdose
Medical Toxicology (1988)