Cigarette smoking and chlorpromazine disposition and actions

Chlorpromazine, 75 mg, was taken by eight cigarette smokers and nine nonsmokers. Mean maximum percent decrease in mean blood pressure with change in position from lying to standing during the first 10 hr after chlorpromazine was 46% greater in nonsmokers than in smokers. Of the eight smokers, six did not become sleepy after chlorpromazine, one became slightly sleepy, and one fell asleep. Of the nine nonsmokers, three became slightly sleepy, one moderately sleepy, and five fell asleep. Mean peak plasma concentration of chlorpromazine was 24% lower and mean area under the plasma concentration-time curve (AUC) was 36% lower in smokers than in nonsmokers. There was no correlation between these plasma level parameters and either the degree of sleepiness or the degree of orthostatic hypotension in the subjects. The relatively small differences between cigarette smokers and nonsmokers in AUCs and peak plasma levels for chlorpromazine, combined with the lack of relationship between these plasma level parameters, the occurrence of drowsiness, and the magnitude of orthostatic hypotension in our subjects make it unlikely that cigarette smoking influenced these effects of chlorpromazine by enhancing its overall metabolism.