Influence of ozone on pentobarbital pharmacokinetics in mice

• Published in: Toxicology letters Vol. 24; no. 2-3; p. 163
• Main Authors: Graham, J A, Menzel, D B, Mole, M L, Miller, F J, Gardner, D E
• Format: Journal Article
• Language: English
• Published: Netherlands 01-01-1985
• Subjects: Animals; Brain - metabolism; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Drug Interactions; Female; Kinetics; Mice; Ozone - pharmacology; Pentobarbital - blood; Pentobarbital - metabolism; Sleep - drug effects
• ISSN: 0378-4274
• DOI: 10.1016/0378-4274(85)90053-0

Previous studies have indicated that acute exposure to ambient concentrations of ozone (O3) as low as 196 micrograms/m3 (0.1 ppm) increases pentobarbital (PEN)-induced sleeping time in female mice. To elucidate potential mechanisms involved, additional studies were performed. A 3 h exposure to 9800 micrograms O3/m3 (5 ppm) did not affect brain concentrations of PEN at time of awakening, even though sleeping time was increased. Exposure for 3 h to 9800 micrograms O3/m3 (5 ppm) did not alter the pattern of brain or plasma metabolites of PEN. Pentobarbital clearance followed first-order kinetics with a one-compartment model. Mice exposed to 9800 micrograms O3/m3 (5 ppm) for 3 h had a 106% increase in the plasma half-life of pentobarbital; at 1960 micrograms O3/m3 (1 ppm) for 3 h, a 71% increase was observed. It therefore appears possible that PEN-induced sleeping time might be increased due to an decrease in hepatic metabolism of PEN.