KINETICS OF ALUMINOXAMINE AND FEROXAMINE CHELATES IN DIALYSIS PATIENTS

To achieve a rational basis for the use of deferoxamine (DFO) in aluminum (AL)- and iron (Fe)-overloaded uremic patients, important insights may be provided by the recently available micromethods to determine DFO and its metallochelates aluminoxamine (AlA) and feroxamine (FeA). With this procedure, AlA and FeA plasma kinetics were evaluated in a pilot study in 10 uremic patients during a whole week after a single DFO infusion performed during the first hour of the first standard bicarbonate hemodialysis (HD) of the week. Patients were divided into normal (n = 6) and high (n = 4) ferritin groups (1 and 2 respectively). Baseline Al concentrations were > 2 < 6 in group 1 and < 1.5-mu-mol/l in group 2. DFO was given at doses of 40, 20 and 10 mg/kg. AlA and FeA showed substantially different kinetics. AlA kinetics were similar in group 1 and 2: they reached their peak at the beginning of the 2nd HD, decreased during the 2nd and 3rd HD, and with the highest DFO dose still increased between the 2nd and 3rd HD. At similar pre-DFO Al values (> 2 < 3.3-mu-mol/l), increased DFO doses produced increased AlA concentrations ranging from 95 to 40% of total plasma Al for all the week. At higher pre-DFO Al values (> 3.5 < 6-mu-mol/l), even a DFO dose as low as 10 mg/kg was sufficient to form consistent AlA amounts (from 80 to 15% of total Al). Also FeA kinetics were similar in group 1 and 2, but in this case, the peak was reached during the first HD, with an ensuing progressive decrease during all the interdialysis periods and HD times. FeA dropped in both groups from about 90-85% to 20-10% of plasma Fe at the beginning of the 2nd HD. A substantial increase in total plasma Fe differentiated group 2 from group 1. Mild differences only were observed with different DFO doses in group 2. Discrepancies between AlA and FeA on one hand, and plasma Al and Fe increase on the other, clearly showed that both circulating Al and Fe contributed to form metallochelates. The implications for clinical practice are that DFO once a week provides substantial Al mobilization and removal and sparse Fe loss in normal iron statues patients, while moderate repeated DFO doses permit Fe removal in iron-overloaded patients.