Over het archief
Het OWA, het open archief van het Waterbouwkundig Laboratorium heeft tot doel alle vrij toegankelijke onderzoeksresultaten van dit instituut in digitale vorm aan te bieden. Op die manier wil het de zichtbaarheid, verspreiding en gebruik van deze onderzoeksresultaten, alsook de wetenschappelijke communicatie maximaal bevorderen.
Dit archief wordt uitgebouwd en beheerd volgens de principes van de Open Access Movement, en het daaruit ontstane Open Archives Initiative.
Basisinformatie over ‘Open Access to scholarly information'.
| one publication added to basket [338237] |
Search for metabolites of ecteinascidin 743, a novel, marine-derived, anti-cancer agent, in man
Sparidans, R.W.; Rosing, H.; Hillebrand, M.J.X.; López-Lázaro, L.; Jimeno, J.M.; Manzanares, I.; van Kesteren, C.; Cvitkovic, E.; van Oosterom, A.T.; Schellens, J.H.M.; Beijnen, J.H. (2001). Search for metabolites of ecteinascidin 743, a novel, marine-derived, anti-cancer agent, in man. Anti-Cancer Drugs 12(8): 653-666. https://hdl.handle.net/10.1097/00001813-200109000-00003
In: Anti-Cancer Drugs. Lippincott Williams & Wilkins: Philadelphia. ISSN 0959-4973; e-ISSN 1473-5741, meer
|  |
| Trefwoord |
|
| Author keywords |
ecteinascidin 729; ecteinascidin 743; high-performance liquid chromatography; metabolism; microsomes |
| Auteurs | | Top |
- Sparidans, R.W.
- Rosing, H.
- Hillebrand, M.J.X.
- López-Lázaro, L.
|
- Jimeno, J.M.
- Manzanares, I.
- van Kesteren, C.
- Cvitkovic, E.
|
- van Oosterom, A.T., meer
- Schellens, J.H.M.
- Beijnen, J.H.
|
| Abstract |
Ecteinascidin 743 (ET-743) is a potent anti-tumoral agent of a marine origin. It is currently being tested in phase II clinical trials using a 3-weekly 24-h i.v. infusion of 1500 μg/m2 and 3-h infusions of 1650 μg/m2. Knowledge of the metabolism of ET-743 is, however, still scarce. In the present study, a qualitative chromatographic discovery of metabolites of ET-743 in man is reported. ET-743 and its demethylated analog ET-729 were incubated at 37°C in the presence of enzyme systems, pooled human microsomes, pooled human plasma and uridine 5′-diphosphoglucuronyltransferase, respectively, in appropriate media. Reaction products were investigated chromatographically using photodiode array and ion spray-mass spectrometric detection (LC-MS). The main reaction products in microsomal incubations of ET-743 resulted from a remarkable breakdown of the molecule. In plasma the drugs were deacetylated, and the transferase did actually yield a glucuronide of both ET-743 and ET-729. In contrast, screening of urine, plasma and bile, collected from patients treated with ET-743 at the highest dose levels, using a sensitive LC-MS assay, did not result in detection of ET-729 and metabolites which were generated in vitro. The urinary excretion of ET-743 in man was lower than 0.7% of the administered dose for a 24-h infusion. |
IMIS is ontwikkeld en wordt gehost door het VLIZ.
