Phase I and pharmacokinetic study of tiazofurin (NSC 286193) administered by 5-day continuous infusion.
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.
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003231:Conjunctivitis / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D009503:Neutropenia / Q000139:chemically induced; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use*; D012263:Ribonucleosides / Q000627:therapeutic use*
D012263:Ribonucleosides; D012254:Ribavirin; C033706:tiazofurin