ACTIVATED OXAZAPHOSPHORINES ARE TRANSPORTED PREDOMINANTLY BY ERYTHROCYTES

Purpose: Oxazaphosphorines are metabolised by a variety of pathways, o ne of which leads to activation and the formation of alkylating compou nds. However, the transport forms conveying activated oxazaphosphorine s to the tumour cell have not been fully characterised. There is incre asing recognition of the importance of the erythrocyte as a carrier of compounds in the circulation, and we have recently described higher c oncentrations of 4-hydroxycyclophosphamide within the erythrocyte comp artment compared to plasma. We have now determined the concentrations of ifosfamide and seven of its metabolites in the plasma and erythrocy tes of patients receiving a six-hour intravenous infusion of ifosfamid e.Patients and methods. Red cells from five patients, receiving a tota l of eight cycles of ifosfamide, were separated from plasma using the MESED instrument, and analysis of red cells and plasma performed using Gas Chromatography-Mass Spectrometry (GC/MS). Results: The concentrat ion of all compounds in the erythrocyte compartment was higher than or equal to those in plasma, and isophosphoramide mustard and carboxyifo sfamide showed a particular affinity for the erythrocyte. The red cell fraction can contain as much as 77% of the total blood concentration of isophosphoramide mustard. Conclusions: Erythrocyte associated isoph osphoramide mustard is an important transport form of activated ifosfa mide. Red cells may have a role in the delivery of activated oxazaphos phorines to tissues.