Efficacy of intramuscular and intraperitoneal deferoxamine for aluminum chelation

Abstract

As intravenous administration of deferoxamine is difficult in home dialysis patients we set out to determine the efficacy of intramuscular (i.m.) and intraperitoneal (i.p.) deferoxamine for removal of aluminum. Patients with serum aluminum levels greater than 90 micrograms/liter were studied in a paired fashion with each patient serving as their own control. Serum and peritoneal fluid aluminum were determined using flameless atomic absorption. In hemodialysis patients 2 g of intravenous deferoxamine increased serum aluminum from 124.7 +/- 32.4 to 415 +/- 192.4 micrograms/liter. One g of deferoxamine given intravenously or intramuscularly resulted in 76.8 +/- 35.3% and 70.4 +/- 23.2%, respectively, of the 2 g i.v. response. The rate at which serum aluminum increased following i.v. deferoxamine infusion was biphasic, with an initial rapid phase lasting 139 minutes followed by a much slower phase. The volume of distribution of aluminum following deferoxamine administration was 12.6 +/- 1.61 and the half life (t1/2) for aluminum removal during hemodialysis was 9.0 +/- 2.0 hours. The increase in serum aluminum following deferoxamine was not due to chelation of erythrocyte aluminum as erythrocyte aluminum remained constant over 24 hours. In patients on continuous ambulatory peritoneal dialysis, 2 g intravenous deferoxamine resulted in the removal of 560 +/- 267 micrograms of aluminum over 24 hours while 2 g deferoxamine given intraperitoneally gave 91 +/- 13% of the intravenous response. Aluminum clearance over 48 hours was twice that for 24 hours for both i.v. and i.p. deferoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminium in Alzheimer?s disease: are we still at a crossroad?

“…It is clear from silver-staining techniques and electron microscopic studies that Al induces normally present protein subunits in neurons to assemble into masses of organized filaments. It has been demonstrated that the process of NFT formation can be partially reversed by initiating intramuscular desferroxamine (a metal chelator) treatment, even after the process of NFT has begun [63]. Al-induced neurofibrillary degeneration in rabbits is accompanied by reduction in serotonin and noradrenaline.…”

Aluminum inhibits erythropoiesis in vitro.

“…1 (33,40); alternatively, aluminumaffected progenitors may not readily proliferate in vitro, or their progeny may be lost due to changes in membrane fragility (17,22). Although aluminum has been detected in erythrocytes (46,47), it has not been found in normoblasts of marrows from aluminum-intoxicated patients (20). Direct specific toxicity and/or interference at the cellular membrane remain possible mechanisms of aluminum-transferrin inhibition, and require further study.…”

Prevention and Treatment of Aluminum Toxicity Including Chelation Therapy: Status and Research Needs

“…Desferrioxamine lacks oral efficacy, so is given by iv, im, or ip injection (Molitoris et al, 1987). This is one of the main driving influences behind the search for alternative chelators.…”