@article {2953,
	title = {PHARMACOKINETICS AND DISTRIBUTION OF TRIS(MALTOLATO)ALUMINUM(III) INTO THE CENTRAL-NERVOUS-SYSTEM},
	journal = {Neurotoxicology},
	volume = {15},
	number = {2},
	year = {1994},
	note = {ISI Document Delivery No.: PB305Times Cited: 4Cited Reference Count: 37},
	month = {Sum},
	pages = {371-378},
	type = {Article},
	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.},
	keywords = {ALUMINUM MALTOL, ALUMINUM NEUROTOXICITY, ALUMINUM PHARMACOKINETICS, ALUMINUM-MALTOLATE, BLOOD-BRAIN-BARRIER, COMPLEXES, DIALYSIS, ENCEPHALOPATHY, EQUILIBRIUM, gallium, INVIVO MICRODIALYSIS, MICRODIALYSIS, permeability, RABBITS, SERUM},
	isbn = {0161-813X},
	url = {<Go to ISI>://A1994PB30500014},
	author = {Allen, D. D. and Orvig, Chris and Yokel, R. A.}
}
@article {2952,
	title = {PHARMACOKINETICS OF ALUMINUM 3-HYDROXYPYRIDIN-4-ONE COMPLEXES - IMPLICATIONS FOR ALUMINUM REDISTRIBUTION SUBSEQUENT TO CHELATION-THERAPY},
	journal = {Toxicology},
	volume = {92},
	number = {1-3},
	year = {1994},
	note = {ISI Document Delivery No.: PK035Times Cited: 14Cited Reference Count: 34},
	month = {Sep},
	pages = {193-202},
	type = {Article},
	abstract = {The pharmacokinetics of selected aluminum-hydroxypyridinone (Al-HP) complexes were determined in rats to better understand the relationship between their disposition and elimination parameters and the safety of HPs in the chelation therapy of Al intoxication. Five complexes were administered as i.v. bolus doses of Al-HP (0.25 mmol/kg Al-0.75 mmol/kg HP). The Al-HP steady state volumes of distribution ranged from 220 to 871 ml/kg, suggesting that each complex distributed out of the vascular compartment (which should have been approximate to 65 ml/kg). Systemic clearances ranged from 189 to 906 ml/h per kg. Elimination half-lives (t(1/2)) and mean residence times ranged from 0.36 to 0.84 and 0.52 to 1.20 h, respectively. The Al-CP20 complex had a short t(1/2) and a midrange volume of distribution. It demonstrated no apparent toxicity, whereas myoclonic seizures were observed after Al-CP22, Al-CP24 and Al-CP94 administration. The most appropriate choice for Al chelation among the HPs tested may be CP20. Characterization of the distribution and elimination of Al-HP complexes improves the understanding of potential toxicity that may be associated with HP therapy of Al intoxication.},
	keywords = {3-HYDROXY-4-PYRIDINONES, 3-HYDROXYPYRIDIN-4-ONES, aluminum, ALUMINUM CHELATION, ALUMINUM TOXICITY, CHELATION, DESFERRIOXAMINE, ENCEPHALOPATHY, gallium, INTOXICATION, INVITRO, IRON CHELATORS, OCULAR TOXICITY, pharmacokinetics, RENAL-FAILURE, SUBCUTANEOUS DEFEROXAMINE},
	isbn = {0300-483X},
	url = {<Go to ISI>://A1994PK03500015},
	author = {Allen, D. D. and Orvig, Chris and Yokel, R. A.}
}
