Kinetics of aluminum in rats. III: Effect of route of administration.
Male Fischer rats received 0.1 mg/kg (bolus) of elemental aluminum as the sulfate salt via the portal (n = 4) or systemic (n = 4) route of administration. Blood and bile were serially sampled over an 8-h period, postadministration. Aluminum was determined by flameless atomic absorption spectrophotometry. Blood aluminum concentrations declined in a monoexponential fashion, with half-lives of 0.7 h (portal) and 1.08 h (systemic) (p less than 0.05). The corresponding systemic clearances were 48.9 +/- 10.6 and 35.1 +/- 3.64 mL/(h.kg) (p less than 0.05). The systemic availability following portal administration was 0.66, indicating a significant "first-pass" effect. Biliary aluminum recovery (% dose) was negligible following both routes [0.83 +/- 0.062% (portal) versus 1.3 +/- 0.22% (systemic), p less than 0.05]. Bile flow decreased approximately 40% (p less than 0.05) immediately upon injection of aluminum via the portal route only; flow remained suppressed throughout the study. This decrease in bile flow was most likely responsible for the lower biliary recovery with this route. In contrast, liver recovery of aluminum at 8-h postadministration was higher with the portal route (65.4 +/- 4.1 versus 39.4 +/- 2.52%). These results show that reported values for oral "bioavailability" of aluminum, often calculated by the standard AUC ratio method, underestimate the true extent of absorption. One mechanism of aluminum-related jaundice observed clinically may be due to cholestasis.
Xu
Z X
ZX
School of Pharmacy, University of Missouri-Kansas City 64108.
Tang
J P
JP
Badr
M
M
Melethil
S
S
D000535:Aluminum / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D001646:Bile / Q000737:chemistry; D004333:Drug Administration Routes; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D000535:Aluminum