Effect of cigarette smoking on phenacetin metabolism

Abstract

Nine nonsmokers and nine individuals who smoked more than 15 Cigarettes per day were administered 900 mg of phenacetin orally, and the concentration of phenacetin in plasma was measured 1, 2, 3.5, and 5 hours after the dose. The plasma levels of phenacetin in the smokers were markedly lower than in the nonsmokers. The plasma levels of unconiugated or total N‐acetyl‐p‐aminophenol in the smokers were the same or only slightly lower than in the nonsmokers, and the ratios of the plasma concentration of total N‐acetyl‐p‐aminophenol to phenacetin were increased severalfold in the smokers. These results indicated that cigarette smoking stimulated the metabolism of phenacetin. To learn whether polycyclic hydrocarbons in cigarette smoke could influence the gastrointestinal metaboli5m of phenacetin, we studied the effects of 3,4‐benzpyrene administration on the metabolism of CILphenacetin by enzymes in the intestinal mucosa of the rat. The data indicated that O‐dealkylation of phenacetin did occur—to a small extent—by an enzyme system in the small intestine, and that the activity of this enzyme system was stimulated by treatment of rats with 3,4‐benzpyrene.