Jul 1, 1976

Effect of 3-methylcholanthrene pretreatment on the bioavailability of phenacetin in the rat

Drug Metabolism and Disposition : the Biological Fate of Chemicals
R M WelchR L Deangelis

Abstract

A thin-layer chromatographic procedure is described for the quantitative determination of phenacetin and acetaminophen in rat plasma. The method was used to determine the effect of 3-methylcholanthrene (3-MC) on the disposition and bioavailability of phenacetin following its oral and iv administration to rats. Pretreatment with 3-MC decreased the plasma half-life of phenacetin, after iv administration, from 28 min to 4.5 min and reduced the systemic bioavailability of phenacetin, after oral administration, from 45% in control rats to 6% in 3-MC-treated rats. By comparing the plasma levels of phenacetin in the portal circulation with those in the peripheral circulation, following the oral administration of phenacetin, it was concluded that the 7-fold reduction in the bioavailability of phenacetin observed in 3-MC treated rats was caused by a marked increase in the metabolism of phenacetin during its first pass through the liver.

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Mentioned in this Paper

Methylcholanthrene
Acamol
Liver
Thin Layer Chromatography
Phenacetin

About this Paper

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