@article {Klippert153, author = {P J Klippert and R J Littel and J Noordhoek}, title = {In vivo O-de-ethylation of phenacetin in 3-methylcholanthrene-pretreated rats: gut wall and liver first-pass metabolism.}, volume = {225}, number = {1}, pages = {153--157}, year = {1983}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {By use of a high-performance liquid chromatographic procedure, phenacetin (acetophenetidin) and its O-de-ethylated metabolite paracetamol (acetaminophen), after hydrolysis of paracetamol conjugates, were simultaneously quantified in arterial plasma of both control and 3-methylcholanthrene-pretreated rats after the i.v., portal vein and intraduodenal administration of phenacetin. 3-Methylcholanthrene pretreatment resulted in enhanced phenacetin disposition as was shown from decreased plasma half-life time, decreased oral availability, increased clearance and a raise in metabolite levels. By constructing plasma concentration-time curves and determining the areas under the curves, it was possible to assess liver and gut wall first-pass metabolism. It is concluded that in 3-methylcholanthrene-pretreated rats the intestine contributes significantly, and predominantly over the liver, to phenacetin first-pass metabolism. In contrast, gut wall metabolism in control rats could not be demonstrated.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/225/1/153}, eprint = {https://jpet.aspetjournals.org/content/225/1/153.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }