Effects of short-term dietary exposure to polychlorinated biphenyls on pharmacokinetics of intravenous pentobarbital in rats.
The intravenous pharmacokinetics of pentobarbital (30 mg/kg as pentobarbital sodium) in rats were studied at 0, 1, 2, 3, and 10 days after pretreatment with 0, 1, 5, 25, and 125 ppm of polychlorinated biphenyls in food. The polychlorinated biphenyls then were removed from the food, and the residual effects of the exposure on pentobarbital pharmacokinetics were studied at 15, 25, 45, and 70 days after initiation of the polychlorinated biphenyl exposure. The pharmacokinetics of pentobarbital were approximated to a one-compartment model. After pretreatment at 2 and 5 ppm for up to 10 days, all pentobarbital pharmacokinetic parameters obtained were comparable to control values. Pretreatment at 125 ppm significantly reduced the biological half-life and raised the total body elimination rate constant, total body clearance, and intrinsic clearance of pentobarbital after a 1-day exposure; all parameters apparently reached a new steady-state value by Days 5--10,. Enhanced pentobarbital elimination at 25 ppm was observed after a 3-day exposure, but, again, the elimination parameters appeared to have reached a steady state after 5--10 days of pretreatment. Upon removal of the polychlorinated biphenyls, the various pharmacokinetic parameters showed a lag phase prior to a gradual return to control values. The study shows that intrinsic clearances rather than total body clearances or half-lives are more appropriate in assessing enzymatic induction in agents undergoing facile liver metabolic clearance that borders on blood flow rate dependency.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D006207:Half-Life; D007275:Injections, Intravenous; D007700:Kinetics; D008099:Liver / Q000187:drug effects; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D010424:Pentobarbital / Q000008:administration & dosage / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D013997:Time Factors
D011078:Polychlorinated Biphenyls; D010424:Pentobarbital