PT - JOURNAL ARTICLE AU - R M Welch AU - C R Hughes AU - R L Deangelis TI - Effect of 3-methylcholanthrene pretreatment on the bioavailability of phenacetin in the rat. DP - 1976 Jul 01 TA - Drug Metabolism and Disposition PG - 402--406 VI - 4 IP - 4 4099 - http://dmd.aspetjournals.org/content/4/4/402.short 4100 - http://dmd.aspetjournals.org/content/4/4/402.full SO - Drug Metab Dispos1976 Jul 01; 4 AB - 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.