Passage of 5'-dFUrd and its metabolites 5-FU and 5-FUH2 to CSF in a clinical phase 1 study.
Lumbar puncture was performed on eight patients in a clinical Phase 1 study of doxifluridine (5'-dFDrd). 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.
D000328:Adult; D000368:Aged; D004341:Drug Evaluation; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged
D005467:Floxuridine; C019389:5-fluorodihydrouracil; D005472:Fluorouracil; C025034:doxifluridine