Passage of 5'-dFUrd and its metabolites 5-FU and 5-FUH2to CSF in a clinical Phase 1 study

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Abstract
Lumbar puncture was performed on eight patients in a clinical Phase I study of doxifluridine (5''-dFUrd). 5''-dFUrd, 5''FU and 5-FUH2 were shown to cross the blood-brain barrier to CSF. The maximal concentrations of 5''-dFUrd and 5-FUH2 were about 1-3% of the maximal concentrations in plasma, and were reached within 1-4 h after the end of iv infusion of 5''-dFUrd. 5-FUH2 showed a marked increase in CSF between 3 and 4 h to about 40-60% of the maximal plasma concentration in 5 of the patients, indicating a possible further increase after 4 h. The relationship between the concentrations of 5''-dFUrd and its metabolites in the CSF, and CNS toxicity is discussed.