tiazofurin and Neutropenia

A phase I and pharmacokinetic study of tiazofurin (NSC 286193), a C-nucleoside that inhibits IMP dehydrogenase, has been completed. The drug was administered by continuous infusion over 5 days. The maximum tolerated dose was 1650 mg/m2 per day, neurological toxicity being the dose-limiting factor. Gastrointestinal and hematological toxicity were mild. A definite relationship exists between dosage and steady-state levels. The plasma clearance was 29.13 (+/- SD 4.05) ml/min per m2. No complete or partial remissions were demonstrated among the 18 patients treated at five dose levels between 550 mg/m2 and 2200 mg/m2 per day.

Topics: Adult; Chromatography, High Pressure Liquid; Conjunctivitis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation; Female; Humans; Kinetics; Male; Middle Aged; Neoplasms; Neutropenia; Ribavirin; Ribonucleosides