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PHARMACOKINETICS AND DISTRIBUTION OF TRIS(MALTOLATO)ALUMINUM(III) INTO THE CENTRAL-NERVOUS-SYSTEM

TitlePHARMACOKINETICS AND DISTRIBUTION OF TRIS(MALTOLATO)ALUMINUM(III) INTO THE CENTRAL-NERVOUS-SYSTEM
Publication TypeJournal Article
Year of Publication1994
AuthorsAllen, DD, Orvig, C, Yokel, RA
JournalNeurotoxicology
Volume15
Pagination371-378
Date PublishedSum
Type of ArticleArticle
ISBN Number0161-813X
KeywordsALUMINUM MALTOL, ALUMINUM NEUROTOXICITY, ALUMINUM PHARMACOKINETICS, ALUMINUM-MALTOLATE, BLOOD-BRAIN-BARRIER, COMPLEXES, DIALYSIS, ENCEPHALOPATHY, EQUILIBRIUM, gallium, INVIVO MICRODIALYSIS, MICRODIALYSIS, permeability, RABBITS, SERUM
Abstract

The maltolate compound of aluminum (Al), tris(maltolato)aluminum(III), has been demonstrated to be quite toxic after central administration and in cell cultures. However, reports of peripheral Al-maltolate administration in vivo demonstrated un impressive neurological effects. We found no reports of Al-maltolate pharmacokinetics or its distribution into the central nervous system (CNS) after systemic administration. In the present study, we evaluated Al pharmacokinetics in serum and Al distribution into brain extracellular fluid (ECF) in rats following Al-maltolate administration. The pharmacokinetic studies revealed that systemic clearance, elimination half-life and mean residence time were 42 (+/- 5) ml/hr/kg, 2.2 (+/- 0.5) hr and 3.1 (+/- 0.7) hr [mean+/-SD), respectively. The steady state volume of distribution (V-ss) for Al-maltolate was 130 ml/kg. This V-ss suggests that Al-maltolate may exhibit limited distribution outside the vascular compartment, which is estimated to be approximate to 80 ml/kg in these rats. Previously, we used microdialysis (MD) probes to assess Al-citrate distribution into the CNS. MD was utilized in the present study to evaluate the CNS distribution of Al as a result of Al-maltolate administration. MD probes were implanted into the frontal cortex (FC) and jugular vein to sample Al from brain and blood ECF, respectively. Al was not measurable in FC MD probe dialysates after a 0.5 mmol/kg Al (as maltolate) bolus, but could be measured after steady state blood and brain ECF Al concentrations had been achieved. The Al brain/blood ra tio calculated from Al-maltolate steady state brain and blood MD samples was 0.04, significantly less than those calculated for other Al salts at equimolar Al doses. The present study suggests that unless it is administered centrally, Al-maltolate might render minimal neurological insult because of its minimal permeation into brain extracellular space. (C) 1994 Intox Press, Inc.

URL<Go to ISI>://A1994PB30500014