Estimation of Statistical Moments for Desferrioxamine and Its Iron and Aluminium Chelates: Contribution to Optimisation of Therapy in Uremic Patients

Abstract

We investigated the best time of administration of desferrioxamine (DFO) with respect to the dialysis session, using the approach of the stochastic dynamic system, integrated with the classical pharmacokinetic models. In the 6 patients studied, the mean arrival times of DFO, aluminoxamine (AlO) and ferrioxamine (FO) were, respectively, 193, 1,350 and 126 min, the mean residence times were 1,048, infinite, 1,190 min, respectively. AlO serum levels reach steady state in a mean time of 7 h and 22 min and remain stable in the interdialytic period. FO achieves a peak at the end of DFO infusion and declines during the interdialytic period. DFO, AlO and FO persist a very long time in the body of the uremic patient, thus the dialysis session should be administered when AlO and FO reach steady state. With a dose of 5-10 mg/kg b.w. of DFO, we propose to start the dialysis 8-12 h after the infusion if the main purpose is to treat Al overload or 2-3 h after the infusion if the main purpose is the treatment of hemosiderosis.

The Role of Chelation in the Treatment of Other Metal Poisonings

“…It is well established that despite DFO administration, if aluminum is bound to transferrin, it is neither dialyzable nor accessible to DFO [31]. One study found that only 1 % of all available serum aluminum was chelated as aluminoxamine (AlO), highlighting the importance of transferrin and other endogenous binding proteins [32]. Third, the potential toxicities of the unbound DFO chelator, as well as the toxicities of both chelates-AlO and ferrioxamine (FO)-must be anticipated.…”

“…Third, the potential toxicities of the unbound DFO chelator, as well as the toxicities of both chelates-AlO and ferrioxamine (FO)-must be anticipated. AlO and FO following DFO administration may persist for long periods, especially in kidney disease [32,33].…”

“…An additional consideration is the timing of chelation. In dialysis patients, it may take 6-8 h to have the chelate ALO appear in significant quantities in the serum [32]. For this reason, DFO is normally given at the end of dialysis prior to the next dialysis session [42,43].…”