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Abstract

In vivo O-de-ethylation of phenacetin in 3-methylcholanthrene-pretreated rats: gut wall and liver first-pass metabolism.

P J Klippert, R J Littel and J Noordhoek
Journal of Pharmacology and Experimental Therapeutics April 1983, 225 (1) 153-157;
P J Klippert
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R J Littel
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J Noordhoek
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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.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 225, Issue 1
1 Apr 1983
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Abstract

In vivo O-de-ethylation of phenacetin in 3-methylcholanthrene-pretreated rats: gut wall and liver first-pass metabolism.

P J Klippert, R J Littel and J Noordhoek
Journal of Pharmacology and Experimental Therapeutics April 1, 1983, 225 (1) 153-157;

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Abstract

In vivo O-de-ethylation of phenacetin in 3-methylcholanthrene-pretreated rats: gut wall and liver first-pass metabolism.

P J Klippert, R J Littel and J Noordhoek
Journal of Pharmacology and Experimental Therapeutics April 1, 1983, 225 (1) 153-157;
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