Determination of fostriecin pharmacokinetics in plasma using high-pressure liquid chromatography assay

Ther Drug Monit. 1994 Apr;16(2):186-90. doi: 10.1097/00007691-199404000-00013.


Fostriecin is an antitumor antibiotic with marked activity against ovarian, breast, and lung cancer cell lines in the human tumor clonogenic assay. The mechanism of cytotoxicity in vivo is unknown; in vitro it has been shown to inhibit macromolecular synthesis, interact with the reduced folate carrier system, and inhibit topoisomerase II. Phase I testing of fostriecin in a daily for 5 days schedule has begun in cancer patients. A high-pressure liquid chromatographic method to measure fostriecin in plasma samples was developed using sulfaquinoxaline as an internal standard and ultraviolet detection (268 nm). The extraction efficiency is 70% and the sensitivity limit is 100 ng/ml. The pharmacokinetics of fostriecin were determined in six rabbits following intravenous injection of 12 mg/m2. The mean distribution space was 4.44 L/m2 and the mean plasma clearance was 302 ml/min/m2. The elimination half-life was 11.95 +/- 8.55 min. All rabbits exhibited a 10-60-fold increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that resolved within 48 h of drug administration.

MeSH terms

  • Alkenes / blood
  • Alkenes / pharmacokinetics
  • Animals
  • Antibiotics, Antineoplastic / blood*
  • Antibiotics, Antineoplastic / pharmacokinetics*
  • Chromatography, High Pressure Liquid / methods*
  • Drug Stability
  • Injections, Intravenous
  • Male
  • Polyenes
  • Pyrones
  • Rabbits
  • Sensitivity and Specificity


  • Alkenes
  • Antibiotics, Antineoplastic
  • Polyenes
  • Pyrones
  • fostriecin