ISSN:
1432-0843
Keywords:
Key words Microsomal metabolism
;
N-dechloroethylation
;
Ifosfamide enantiomers
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The cumulative urinary excretions of the enantiomers of ifosfamide [(R)-IFF, (S)-IFF)] and their 2-N-dechloroethylated (2-DCE-IFF) and 3-N-dechloroethylated (3-DCE-IFF) metabolites were determined in 11 adult cancer patients who received a single 3-h infusion of IFF (3 g/m2) with mesna uroprotection. The urine samples were analyzed for the compounds of interest using an enantioselective gas chromatographic- mass spectrometric assay. The results indicated an enantioselective excretion of the parent and N-dechloroethylated metabolites: the urinary recovery of (R)-IFF was significantly greater than that of (S)-IFF (1.73± 0.45 vs 1.43±0.41 mmol, P〈0.0001); the excretion of (S)-2-DCE-IFF (0.75±0.53 mmol) was greater than that of (R)-2-DCE-IFF (0.42± 0.22 mmol, P=0.071) while the excretion of (R)-3-DCE-IFF (1.64± 0.76 mmol) was greater than that of (S)-3-DCE-IFF (0.77±0.59 mmol, P=0.012). The study also revealed two distinct metabolic patterns in which the urinary recoveries of (R)-2-DCE-IFF and (R)-3-DCE-IFF were linked as were those of (S)-2-DCE-IFF and (S)-3-DCE-IFF. The results suggest that at least two enzymes are involved in the N-dechloroethylation of IFF. The data also demonstrate the importance of following the metabolic fate of (R)-IFF and (S)-IFF and of determining the relative urinary excretion of all dechloroethylated metabolites.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002800050393
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