Pharmacokinetics and bioavailability of pyrene in the rat

Abstract

Groups of 6 male Wistar rats, of about 400 g body weight, were dosed with ¹⁴C‐labeled pyrene, dissolved in an Emulphor/water solvent vehicle, at 5 different dose levels by the intravenous or oral routes. Appropriate mathematical models were fitted to blood concentration‐time data for [¹⁴C]pyrene and pyrene per se and dose‐trend analyses were carried out. Areas under these curves were used to assess the bioavailability of the orally administered doses. Tissue concentrations, measured at the termination of the blood sampling period, gave a quantitative measure of the distribution of the administered dose. Attempts to repeat these studies with similar doses of tritium‐labeled benzo[a]pyrene were frustrated by the lack of meaningful blood‐level data.

Dose trends for the derived pharmacokinetic parameters for pyrene revealed that the kinetics were nonlinear and strongly suggestive of enterohepatic recycling. Biliary excretion, measured in a separate experiment, gave support to this hypothesis. The bioavailability of the orally administered doses was between 50 and 60%. Over a 6‐d period postdosing, some 45 and 40% of the administered dose was excreted via the urine and feces, respectively, irrespective of the route of administration. Distribution to the tissues of the ¹⁴C‐label was highest in the perirenal fat, intermediate in the liver, kidneys, and lungs, and lowest in the heart, testes, spleen, and brain.