Effect of short-term exposure to polychlorinated biphenyls on first-pass metabolism of pentobarbital in rats.

The enhancement of the first-pass metabolism of orally administered pentobarbital in rats was examined after a 10-day exposure to food contaminated with polychlorinated biphenyls at 25 and 125 ppm. The degree of the first-pass effect and the influence of the polychlorinated biphenyl exposure were quantitated by comparing the areas under the plasma concentration--time curves after oral and intravenous dosing in control and treated animals. By using the clearance model and assuming that pentobarbital was eliminated totally by liver metabolism, the experimentally determined oral availability was predicted adequately from both the oral and intravenous data. The enhanced first-pass effect was principally in the intrinsic clearance term, although liver blood flow rates also appeared to be enhanced in animals treated with polychlorinated diphenyls at 125 ppm.