Date of Graduation
The present study was designed to examine: (1) the absorption and disposition of aluminum in rats following intravenous and oral doses of aluminum as aluminum chloride; (2) the effects of renal failure on absorption and disposition of aluminum in rats following intravenous and oral doses of aluminum as aluminum chloride; and (3) dose dependent plasma protein binding and disposition of aluminum in rats following intravenous doses equivalent to 4.05, 8.1 and 24.3 mg/kg aluminum as aluminum chloride. In the first section of the study, intravenous bolus and oral doses of 8.1 mg/kg aluminum were administered as the chloride salt to 6 rats. Serial blood samples and total urine feces were collected and assayed for aluminum by atomic absorption spectrophotometry. The fraction absorbed orally (mean (+OR-) SEM) was 0.27 (+OR-) 0.03; half-life, 5.20 (+OR-) 0.47 hours; steady-state volume of distribution, 38.4 (+OR-) 6.4 mL/kg and total body clearance 8.87 (+OR-) 1.76 mL/h.kg. Aluminum did not significantly penetrate the cellular components of blood. Plasma protein binding was approximately 98%. Finally 60% of the intravenous dose was excreted with 75% being reabsorbed by the kidneys. The remaining 40% of the dose was excreted in the feces. In the second section of the study, the kinetics of aluminum were determined in normal and renally imparied rats. Renal impairment was caused by the intravenous injection of uranyl nitrate. In rats with renal failure compared to those with normal kidney function (1) aluminum absorption was considerably delayed but the extent of absorption was not altered; (2) protein binding was decreased although the steady-state volume of distribution was unaffected; and (3) both non-renal and renal clearance were reduced. In the last section of the study, the plasma protein binding and the kinetics of aluminum were determined following intravenous doses equivalent to 4.05, 8.1 and 24.3 mg/kg aluminum as aluminum chloride. Protein binding, volume of distribution, renal and non-renal clearance and half-life were varied significantly with dose. The unbound volume of distribution and unbound renal and non-renal clearance showed much less variability with dose suggesting that does dependent changes in aluminum kinetics can be attributed to saturable plasma protein binding.
GUPTA, SAMIR KUMAR, "ABSORPTION AND DISPOSITION OF ALUMINUM IN RATS WITH NORMAL AND EXPERIMENTALLY IMPAIRED RENAL FUNCTION." (1986). Graduate Theses, Dissertations, and Problem Reports. 8968.