Cigarette smoking and chlorpromazine disposition and actions

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Abstract
Chlorpromazine 75 mg was taken by 8 cigarette smokers and 9 nonsmokers. Mean maximum percent decrease in mean blood pressure with change in position from lying to standing during the first 10 h after chlorpromazine was 46% greater in nonsmokers than in smokers. Of the 8 smokers, 6 did not become sleepy after chlorpromazine, 1 became slightly sleepy and 1 fell asleep. Of the 9 nonsmokers, 3 became slightly sleepy, 1 moderately sleepy and 5 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 AUC 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 the subjects make it unlikely that cigarette smoking influenced these effects of chlorpromazine by enhancing its overall metabolism.