Effect of protein deficiency and Tween 60 on the pharmacokinetics of butylated hydroxyanisole and metabolites in male Sprague-Dawley rats.

Abstract

Radioactive 3H-butylated hydroxyanisole (BHA) at dosages of 250 or 2,500 mg/kg body weight was administered to rats either orally (po) or intraperitonealy (ip) with or without 500 mg Tween 60/kg. The pharmacokinetics of 3H-BHA were evaluated in both control and protein-deficient animals. Blood or urine and feces were collected and analyzed for 3H-BHA equivalents. Using the Autoan/Nonlin69 computer program, most pharmacokinetic profiles of BHA (250 mg/kg) were fit to one-compartment open models with first-order absorption. The exception was the model for ip administration, which resulted in a two-compartment open model with first-order absorption. Increasing the dose of BHA to 2,500 mg/kg altered pharmacokinetics of BHA; no decline in blood levels was observed 48 hours post-injection. Protein deficiency and Tween 60 in combination increased the rate of absorption of BHA. Excretion of 3H-BHA and/or its metabolites in urine and feces was complete 6.5 days after administration of 2,500 mg/kg 3H-BHA.