Metabolische umwandlung von phenacetin und N-acetyl-p-aminophenol nach vorbehandlung mit phenobarbital

Pretreatment of rats with phenobarbital activates the metabolism of acetophenetidin and of N -acetyl- p -aminophenol (NAPAP). The O -desalkylation of acetophenetidin and the conjugation of NAPAP with glucuronic acid are increased. These results were obtained by measuring the serum levels and by controlling the excretion of acetophenetidin, NAPAP and its conjugates in the urine. After administration of high doses of acetophenetidin in induced animals an increased concentration of methemoglobin was detected which indicates that the desacetylation and the N -hydroxylation are stimulated. Therefore pretreatment with phenobarbital in rats not only causes an enhanced detoxication of acetophenetidin, but also under high doses of acetophenetidin leads to an increase in its toxicity. The augmented conjugation of NAPAP after phenobarbital pretreatment, however, accelerates exclusively the detoxication.