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.
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Authors | L Pillon, M J Moore, J J Thiessen |
Journal | Therapeutic drug monitoring
(Ther Drug Monit)
Vol. 16
Issue 2
Pg. 186-90
(Apr 1994)
ISSN: 0163-4356 [Print] United States |
PMID | 8009568
(Publication Type: Journal Article)
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Chemical References |
- Alkenes
- Antibiotics, Antineoplastic
- Polyenes
- Pyrones
- fostriecin
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Topics |
- Alkenes
(blood, pharmacokinetics)
- Animals
- Antibiotics, Antineoplastic
(blood, pharmacokinetics)
- Chromatography, High Pressure Liquid
(methods)
- Drug Stability
- Injections, Intravenous
- Male
- Polyenes
- Pyrones
- Rabbits
- Sensitivity and Specificity
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