Smoking and warfarin disposition

Nine cigarette smokers ingested an average daily 0.032 mg/kg dose of sodium warfarin for 2 wk while continuing to smoke and for an additional 2 wk after having abstained from cigarette smoking for a month washout phase. Steady-state plasma levels of warfarin, clearances, t 1/2, apparent volumes of distribution, steady-state prothrombin times, and plasma thiocyanate levels were measured during both the smoking and nonsmoking phases. During the nonsmoking phase there was a 13% increase in average steady-state warfarin level and a 13% decrease in warfarin clearance rate. There also was a 23% increase in warfarin t 1/2 and an 11% increase in the apparent volume of distribution. Prothrombin time did not change. Thiocyanate levels were 3 to 4 times as high during the smoking than the nonsmoking phase. It appears that cigarette smoking does affect warfarin clearance, t 1/2, and apparent volume of distribution, though the net effect on warfarin's pharmacodynamic activity is negligible, at least at doses which are ineffective therapeutically.