title: Determination of fostriecin pharmacokinetics in plasma using high-pressure liquid chromatography assay.
abstract: 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.
authors.affiliation: Faculty of Pharmacy, University of Toronto, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Pillon
authors.forename: M J
authors.initials: MJ
authors.lastname: Moore
authors.forename: J J
authors.initials: JJ
authors.lastname: Thiessen
mesh_terms: D000475:Alkenes / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000097:blood* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D007275:Injections, Intravenous; D008297:Male; D011090:Polyenes; D011753:Pyrones; D011817:Rabbits; D012680:Sensitivity and Specificity
chemical_list: D000475:Alkenes; D000903:Antibiotics, Antineoplastic; D011090:Polyenes; D011753:Pyrones; C040313:fostriecin