Influence of ozone on pentobarbital pharmacokinetics in mice.
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.
D000818:Animals; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D007700:Kinetics; D051379:Mice; D010126:Ozone / Q000494:pharmacology*; D010424:Pentobarbital / Q000097:blood / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects*
D010126:Ozone; D010424:Pentobarbital