Oxidative biotransformation of the antitumour agent elliptinium acetate: Structural characterization of its human and rat urinary metabolites.
The electrophilic properties of the antitumour drug N(2)-methyl-9-hydroxyellipticinium acetate (Celiptium) are revealed by the detection of thiol-conjugate metabolites in man and rat urine. Besides the unchanged drug and its glucuronide, the cysteinyl- (in man) and the N-acetylcysteinyl- (in man and rat) conjugates have been unambiguously characterized using NMR, UV and mass spectral data. The urinary excretion profile exhibits total excreted products of 21% (in man) and 9% (in rat) with respect to the administered dose. The unchanged drug is found to be the major excreted compound from urine in both species (17% in man, 6.3% in rat); whereas the glucuronide (2.6% in man, 1.5% in rat), cysteinyl- (1.3% in man) and N-acetylcysteinyl- (0.2% in man, 1.2% in rat) conjugates represent the minor excreted compounds. The presence of the latter thio-conjugates provides an indirect proof of the in vivo generation of an oxidized intermediate form of the administered drug.
Monsarrat
B
B
Laboratoire de Pharmacologie et Toxicologie Fondamentales du CNRS, 205 route de Narbonne, 31400 Toulouse, France.
Maftouh
M
M
Meunier
G
G
Bernadou
J
J
Armand
J P
JP
Paoletti
C
C
Meunier
B
B