PHARMACOKINETICS OF AND CYP1A INDUCTION BY PYRIDINE AND ACETONE IN THE RAT - INTERACTIONS AND EFFECTS OF ROUTE OF EXPOSURE

1. Male Sprague-Dawley rats were exposed to either pyridine, acetone o r a combination of both compounds by either intraperitoneal administra tion (100 mg/kg pyridine or 400 mg/kg acetone) or whole-body inhalatio n (200 ppm pyridine or 1000 ppm acetone). Plasma and tissue levels of both compounds were determined by gas chromatography/mass spectrometry . 2. Both chemicals were well distributed in the tissues examined foll owing either route of exposure, with concentrations in the order kidne y > liver > plasma > lung. 3. Plasma half-life of pyridine was 17 h fo llowing a single 100 mg/kg dose of the compound, and 8 h following the last dose of a 3-day, 8 h/day exposure to a 200 ppm inhalation dose o f the compound. 4. Plasma half-life of acetone was 4 h, and was indepe ndent of the route of exposure. 5. The pharmacokinetics of pyridine wa s not affected by co-exposure to acetone. Similarly, the pharmacokinet ics of acetone was not affected by co-exposure to pyridine. 6. Ethoxyr esorufin O-deethylase activity in lung and liver and methoxyresorufin O-demethylase activities in liver were induced by pyridine but not by acetone at the doses examined. Pyridine-induced ethoxyresorufin O-deet hylase activity was higher following inhalation exposure than followin g i.p. administration of pyridine but did not parallel tissue levels o f the compound.