Pharmacokinetics of low doses of benzo[a]pyrene in the rat

Intestinal absorption, bioavailability, hepatic and pulmonary extraction and elimination of low doses of benzo[a]pyrene (BP; 0.7-4.4 nmol) were studied in the rat using [G-3H]BP. The hepatic extraction ratio was 0.4 both in a liver perfusion model and in vivo as determined by comparison of intravenous and intraportal infusion experiments in anaesthetized rats. The pulmonary extraction ratio in vivo was 0.11 in control rats and 0.16 in rats pretreated with an inducer of cytochrome P-448. Analysis of BP concentrations in atrial blood and in the bile after continuous BP infusion into the duodenum of anaesthetized rats indicated that at least 30% of the dose must have been absorbed from the gut. Studies have also been performed in conscious rats given BP either as an intravenous bolus or by gavage. The bioavailability was determined to be about 10% in these experiments. Elimination proceeded in a triphasic manner with a half-life of 16.6 hr for the terminal phase.