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 or a combination of both compounds by either intraperitoneal administration (100 mg/kg pyridine or 400 mg/kg acetone) or whole-body inhalation (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 following either route of exposure, with concentrations in the order kidney > liver > plasma > lung. 3. Plasma half-life of pyridine was 7 h following 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 of the compound. 4. Plasma half-life of acetone was 4 h and was independent of the route of exposure. 5. The pharmacokinetics of pyridine was not affected by co-exposure to acetone. Similarly, the pharmacokinetics of acetone was not affected by co-exposure to pyridine. 6. Ethoxyresorufin 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-deethylase activity was higher following inhalation exposure than following i.p. administration of pyridine but did not parallel tissue levels of the compound.
Scholl
H R
HR
Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ 08855, USA.
Iba
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MM
D000096:Acetone / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000280:Administration, Inhalation; D000818:Animals; D019540:Area Under Curve; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D007274:Injections, Intraperitoneal; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014018:Tissue Distribution
D011725:Pyridines; D012997:Solvents; D000096:Acetone; D006899:Mixed Function Oxygenases; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; C023666:pyridine