Kinetics of aluminum in rats. II: Dose-dependent urinary and biliary excretion.
Previous iv studies from our laboratories have shown that the disappearance half-life of blood aluminum increased with dose. Experiments were initiated to determine if saturation of biliary and/or urinary excretion could be responsible for this dose-dependent behavior. Biliary aluminum excretion (0-12 h) accounted for less than 1% of the injected amount at 0.1- and 1.0-mg/kg doses. During the same interval, urinary excretion accounted for 16.7 +/- 2.66 and 8.85 +/- 2.2% of administered dose at the low and high doses, respectively (p less than 0.05); corresponding long term (0 to 13 or 22 days) urinary recoveries were 37.6 +/- 3.67 and 28.4 +/- 1.88% of the injected dose (p less than 0.05), with most (66-70%) of the excretion occurring in the first 24 h. This is consistent with many previous reports showing that urinary excretion is one major elimination pathway for aluminum. Both biliary and urinary clearances decreased with increasing blood aluminum concentration; the biliary and urinary clearance values at low concentrations (500-900 ng/mL) were approximately four- and threefold higher than the corresponding values at higher concentrations (10,000-12,000 ng/mL), respectively. It appears that this apparent saturability of biliary clearance may be due to concentration-dependent of transfer from blood to liver, rather than from liver to bile. In vitro ultrafiltration studies support the hypothesis that decreases in urinary clearance were due to decreased filterability of aluminum at the glomerulus as its blood concentration was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Xu
Z X
ZX
University of Missouri-Kansas City, School of Pharmacy 64108-2792.
Pai
S M
SM
Melethil
S
S
D000535:Aluminum / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D001646:Bile / Q000378:metabolism*; D006207:Half-Life; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014462:Ultrafiltration
D000535:Aluminum