Disease relevance of Ifosforamide mustard

• Both inactive IFO and active IPM cross the blood-brain barrier, making IFO treatment effective in the prevention of CNS metastasis in lymphoma patients at high risk of recurrence [1].

High impact information on Ifosforamide mustard

• The production of two major metabolites, aldoifosfamide and isophosphoramide mustard, by mice hepatic microsomes from non-tumor-bearing female CBA/CaJ mice was also investigated [2].
• A sensitive method, based on gas chromatography using a phosphorus-specific flame photometric detector, has been developed for quantifying N,N'-di-(2-chloroethyl)phosphorodiamidic acid (isophosphoramide mustard), the putative active metabolite of isophosphamide, in human plasma [3].
• Peak plasma levels of isophosphoramide mustard of 18.6 to 30.3 nmol/ml occurred at 2 to 4 hr, and levels were still appreciable (6.3 to 11.3 nmol/ml) at 24 hr [3].
• 31P nuclear magnetic resonance spectroscopy was used to measure the pKa (4.28 +/- 0.2) of isophosphoramide mustard (IPM) at 20 degrees C and to study the kinetics and products of the decomposition of IPM at a solution pH value of ca. 7.4 and at temperatures between 20 and 47 degrees C in the presence of nucleophilic trapping agents [4].
• Ifosfamide (IFO) is a widely used antitumor agent, requiring activation to isophosphoramide mustard (IPM) for DNA alkylation [1].

Biological context of Ifosforamide mustard

• To investigate the role of 1,5-intramolecular cyclizations in the chemistry of IPM and PM, the five-membered ring phospholidine products of these reactions were independently synthesized and characterized by (31)P NMR [5].
• RESULTS: The area under the plasma concentration-time curve (AUC) for ifosfamide increased linearly with dose while the AUC's of the metabolites measured in plasma by thin-layer chromatography did not increase with dose, particularly that of the active metabolite isophosphoramide mustard [6].
• Isophosphoramide mustard and 2-chloroethylamine, a potential hydrolysis product of isophosphoramide mustard and carboxyifosfamide, were less mutagenic in the standard Ames test than the 2 corresponding metabolites of cyclophosphamide [phosphoramide mustard and bis(2-chloroethyl)amine] [7].
• Preclinical pharmacokinetics and stability of isophosphoramide mustard [8].
• Comparative preclinical toxicology and pharmacology of isophosphoramide mustard, the active metabolite of ifosfamide [9].

Anatomical context of Ifosforamide mustard

• RESULTS: The concentration of all compounds in the erythrocyte compartment was higher than or equal to those in plasma, and isophosphoramide mustard and carboxyifosfamide showed a particular affinity for the erythrocyte [10].

Gene context of Ifosforamide mustard

• Two types of prodrugs, benzyl analogues of isophosphoramide mustard (iPAM), activated by cytochrome P450, and acylthioethyl analogues, activated by esterases, were designed [11].

References