Effect of 3-methylcholanthrene pretreatment on the bioavailability of phenacetin in the rat.
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.
D000082:Acetaminophen / Q000097:blood*; D000818:Animals; D001682:Biological Availability; D002855:Chromatography, Thin Layer; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D010615:Phenacetin / Q000097:blood / Q000378:metabolism*; D051381:Rats
D000082:Acetaminophen; D008748:Methylcholanthrene; D010615:Phenacetin