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. 1983 Nov;48(5):705-10.
doi: 10.1038/bjc.1983.253.

Pharmacokinetic rationale for the interaction of 5-fluorouracil and misonidazole in humans

B J McDermott, H W Van den Berg, W M Martin, R F Murphy
Free PMC article

Pharmacokinetic rationale for the interaction of 5-fluorouracil and misonidazole in humans

B J McDermott et al. Br J Cancer. 1983 Nov.
Free PMC article

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.

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