Influence of renal impairment, chemical form, and serum protein binding on intravenous and oral aluminum kinetics in the rabbit.
The influence of renal impairment on the intravenous kinetics of aluminum (Al) lactate and the oral absorption of eight representative Al forms was determined. The serum protein binding of Al was assessed. Creatinine clearance in renally impaired rabbits was 23% of controls. Systemic clearance of Al was less in renally impaired rabbits (39 vs. 53 ml/hr/kg), as were the steady-state volume of distribution (516 vs. 1175 ml/kg), the half-life of elimination (14 vs. 27 hr), and the mean residence time of Al (14 vs. 25 hr). The shorter Al half-life and mean residence time in renally impaired rabbits were due to a diminished volume of Al distribution. Oral bioavailability of Al in renally intact rabbits ranged from 0.3 to 2.2% (Al borate less than glycinate less than hydroxide less than chloride less than sucralfate less than lactate less than nitrate less than citrate). Renal impairment had little influence on oral bioavailability of most Al forms, although it increased Al citrate absorption to 4.6%. In vitro and in vivo determination of Al ultrafilterability (less than 30,000 D) as an estimate of serum protein binding suggested a greater percentage of ultrafilterable Al species in renally impaired rabbit serum than in control rabbit serum. The increase in ultrafilterable Al species produced the less than expected reduction in Al clearance in renally impaired rabbits. The ultrafilterability of various Al concentrations was greater for citrate greater than lactate greater than nitrate greater than chloride, perhaps partially explaining the similar rank order of oral absorption of these Al forms. The physicochemistry of the eight Al forms was further characterized by determination of their octanol/water partitioning coefficients and their water solubility. There was a significant correlation between the percentage absorbed and the log of the octanol/water partition coefficient. Knowledge of the physicochemistry of Al aids in the understanding of Al pharmacokinetics.
Yokel
R A
RA
College of Pharmacy, University of Kentucky, Lexington 40536-0082.
McNamara
P J
PJ
D000284:Administration, Oral; D000535:Aluminum / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007674:Kidney Diseases / Q000378:metabolism*; D000442:Octanols; D011485:Protein Binding; D011817:Rabbits; D012995:Solubility; D014462:Ultrafiltration
D001798:Blood Proteins; D000442:Octanols; D003404:Creatinine; D000535:Aluminum