Phase I trial and pharmacokinetics of a daily x 5 schedule of 3-deazauridine.
The uridine analog 3-deazauridine has been given to 19 patients in a phase I and pharmacokinetic study. Only mild toxicity was seen at doses less than 1200 mg/m2/day for 5 days. At a dose of 1200 mg/m2/day x 5, leukopenia (mean wbc count nadir of 2650/mm3) was seen in nine of 12 patients and thrombocytopenia (mean platelet count nadir of 47,000/mm3) in five of 12 patients. Nausea and vomiting and oral toxicity were each seen in two patients, and diarrhea and skin toxicity occurred in one patient each. Pharmacokinetic studies indicate a biphasic plasma decay with a beta-half-life of 6.9 hours and urinary excretion, mostly of unchanged drug, as the most important route for drug elimination. A dose of 1200 mg/m2/day x 5 is recommended for phase II studies and great caution is advised in administering the drug in the presence of renal impairment.
D015092:3-Deazauridine / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D002675:Child, Preschool; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007700:Kinetics; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D013921:Thrombocytopenia / Q000139:chemically induced; D014529:Uridine / Q000031:analogs & derivatives*
D015092:3-Deazauridine; D014529:Uridine