Pharmacokinetics and renal elimination of desferrioxamine and ferrioxamine in healthy subjects and patients with haemochromatosis.

Abstract

1 Desferrioxamine mesylate (DM) (10 mg kg‐1 = 15.24 mumol kg‐1) was given by intramuscular injection to five healthy subjects and to six patients with haemochromatosis, after informed consent. 2 Desferrioxamine (DFA), ferrioxamine (FeA), aluminoxamine (AlA), aluminium (Al) and iron (Fe) were measured in plasma, before and 10, 20, 30, 60 min and 2, 4, 6, 8, 12 h after DM injection and in urine collected over a 6 h period the day before and the day of administration. 3 The predominant form in plasma from control subjects was DFA whereas FeA predominated in plasma from patients. In controls, rapid and slow phases of decline in plasma DFA concentrations were found, with half‐lives of 1.0 h and 6.1 h, respectively. In the patients, only a single phase of decline was observed, with a half‐life of 5.6 h. Total clearances of DFA were 296 ml h‐1 kg‐1 in controls and 239 ml h‐1 kg‐1 in patients. 4 The amount of FeA eliminated in urine during 6 h was significantly lower in controls (8.0 +/‐ 4.6 mumol) than in patients (129.2 +/‐ 40.0 mumol), with respective renal clearances estimated over 6 h of 516 ml h‐1 kg‐1 and 1,716 ml h‐1 kg‐1. DFA elimination was similar in both groups and its renal clearance estimated over 6 h was 91 ml h‐1 kg‐1 in controls and 85 ml h‐1 kg‐1 in patients. 5 Since there was no overlap in the 1 h DFA/FeA plasma ratio between controls and patients, this might be useful as an index of iron overload.

Development of an Intravenous Desferrioxamine Mesylate Treatment Protocol for Swine: Monitoring of Desferrioxamine and Metabolites by High-Performance Liquid Chromatography

“…The elimina tion parameters of the parent drug (ti/j; ta ble 2) show one phase of decline. The elimi nation kinetics of the latter pigs agree with those reported by Allain et al [21] in pa tients with hemochromatosis where the par ent drug measured in plasma was primarily in the form of FO, and the DFO and FO elimination kinetics showed one phase of decline.…”

Kinetics of Aluminoxamine and Feroxamine Chelates in Dialysis Patients

“…Our results confirm those observed in healthy people, patients with hemochromatosis and in uremic patients [22,33]. In pa tients with normal Fe status, there is no substantial Fe mobilization from tissue stores, and most Fe recruited to form FeA must thus come from circulating Fe.…”

“…Therefore, no advantage in reducing Fe loss seems to be provided by delaying the first dialysis session after DFO infusion. After the first HD, FeA concentrations decline during the interdialysis periods, probably as the net result of removal via the hepatic and biliary excretion, which is not balanced by a proportional formation of new chelate [33][34][35], This continuous decrease of the free diffus ible chelated form accounts for a reduced Fe removal in the following HD, as previously shown in a study of Fe mass transfer during a whole week following a single DFO infu sion [37], Furthermore, it is worth noting that repeated DFO infusion should increase Fe waste, because during the first post-DFO HD FeA concentrations are at their maximum level.…”

“…Previous studies have demonstrated the ability of DFO to remove Fe from transferrin other than from other exchangeable pools [34][35][36], In these cases, the intradialysis removal of the free diffusible FeA is an unwanted side effect of DFO treatment for Al overload, and FeA kinetics may therefore help to understand how this loss may be minimized. As it has been demonstrated that the peak achieved at the end of DFO infusion remains unchanged for the next 48 h if HD is delayed [33], the intradialysis removal should be similar if HD is performed immediately after the peak is reached, or 48 h after. Therefore, no advantage in reducing Fe loss seems to be provided by delaying the first dialysis session after DFO infusion.…”

Effects of an EDTA infusion on the urinary elimination of several elements in healthy subjects.

“…In conclusion, like the desferrioxamine test that we studied recently (Allain et al, 1987), the EDTA Ca Na2 test can be useful in the diagnosis and treatment of intoxication by some elements. The present data from healthy subjects forms a basis for the quantitative evaluation of the results of the EDTA Ca Na2 test.…”