942 Uptake of ifosfamide (IF) and its metabolites by erythrocytes (E)

IF is a prodrug requiring activation to isophosphoramide mustard (IPM), but the main site of formation of IPM and its circulating transport form are not certain. We have recently described an instrument (MESED) † allowing the separation and simultaneous analysis of E and plasma(P) fractions, and present the results of such an analysis in two patients receiving an infusion of IF 3 g m −2 over 6 hours. Blood was sampled until approx. 24 hrs after the infusion; E and P fractions were separated immediately using MESED; and IF and its metabolites measured with GC-MS. High mean E/P Cmax ratios were seen for IPM (5.94), Carboxyifosfamide (4.28), Ketoifosfamide (2.87) and IF (2.26), and lower ratios for 2- and 3-Dechloroethylifosfamide, Chloroethylamine and 1,3-Oxazolidine-2-one (1.17–1. 83). E/P AUC ratios showed a similar trend. Therefore, there is significant uptake of IF and its metabolites, particularly IPM, by E, which may be important in the transfer and delivery of these compounds.