Decreased concentration of phenacetin in plasma of cigarette smokers

The amount of phenacetin in plasma was determined in nine control subjects (nonsmokers) and nine subjects who smoked at least 15 cigarettes per day. The mean plasma concentration of phenacetin at 1, 2, 3(1/2), and 5 hours after its administration was markedly lower in cigarette smokers than in nonsmokers. At 2 hours after the oral administration of 900 milligrams of phenacetin, the plasma concentration (+/- standard error) of unchanged drug was 2.24 +/- 0.73 micrograms per milliliter in the controls and 0.48 +/- 0.28 micrograms per milliliter in the smokers. The rate of excretion in urine of the major metabolite of phenacetin, N-acetyl-p-aminophenol, was the same in both groups. These results indicate for the first time decreased concentrations of a drug in plasma of persons who smoke cigarettes, and the results suggest that the decrease in the amount of Phenacetin in plasma may result from increased metabolism of phenacetin in cigarette smokers.