Disposition of phenacetin in rabbits pretreated orally and intraperitoneally with 3,4-benzpyrene.

Disposition of phenacetin (PHT) administered intravenously was investigated in rabbits pretreated orally and intraperitoneally with 3,4-benzpyrene. 3,4-Benzpyrene pretreatment intraperitoneally 24 and 48 h before the disposition experiments resulted in enhanced PHT metabolism as was shown from the decreased levels of PHT and the increased levels of acetaminophen sulfate (NAPAS) in the blood after intravenous administration of PHT. Following the oral pretreatment with 3,4-benzpyrene 24 h before the disposition experiments, no effect was found on the metabolism of PHT compared to the control. 3,4-Benzpyrene pretreatment orally 48 h before the disposition experiments resulted in enhanced PHT metabolism as was shown from the decreased levels of PHT and the increased levels of acetaminophen glucuronide and NAPAS in the blood. From these results, the response to oral and intraperitoneal pretreatment with 3,4-benzpyrene appears to be profoundly different. A technique for selective enzyme induction in the intestine by the route of administration of inducer is discussed.