| Autor: |
R, Martino, F, Crasnier, N, Chouini-Lalanne, V, Gilard, U, Niemeyer, M, De Forni, M C, Malet-Martino |
| Rok vydání: |
1992 |
| Předmět: |
|
| Zdroj: |
The Journal of pharmacology and experimental therapeutics. 260(3) |
| ISSN: |
0022-3565 |
| Popis: |
[31P] nuclear magnetic resonance spectroscopy was used to analyze body fluids from patients treated with ifosfamide (IF). This technique, which requires no labeled drug, allows a direct study of the biological sample with no need for extraction or derivatization and a simultaneous detection and quantification of all the different phosphorated metabolites in a single analysis. In urine, isophosphoramide mustard was detected in addition to the already known human urinary compounds [i.e., unchanged IF, carboxyifosfamide, 2-dechloroethylifosfamide, 3-dechloroethylifosfamide, ketoifosfamide]. 2,3-Didechloroethylifosfamide itself was not found, but two of its degradation compounds were detected, thus showing a minor route of didechloroethylation of IF in humans. Several other signals corresponding to unknown metabolites or to degradation compounds of IF metabolites were observed. None of them corresponded to IF-activated metabolites (4-hydroxyifosfamide, aldoifosfamide) or to conjugates of IF or its metabolites with mesna. The urinary excretion of IF and metabolites over 24 h amounted to 39 to 50% of the injected dose. Unmetabolized IF was the major compound in 0- to 8-h and 8- to 16-h fractions. 2-Dechloroethylifosfamide and 3-dechloroethylifosfamide were the main metabolites detected in each 8-h fraction. The two unknown compounds at 19.16 ppm and 16.06 ppm represented a non-negligible fraction of the excretion, above that of carboxyifosfamide. Only unchanged IF could be detected in plasma samples. Unmetabolized IF and 3-dechloroethylifosfamide were found in a cerebrospinal fluid sample. Neither IF nor IF metabolites could be observed in the corresponding plasma sample. This indicates a long persistence of these compounds in cerebrospinal fluid. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
