Cotinine disposition and effects

Abstract

Cotinine is the major metabolite of nicotine in man. Cotinine disposition kinetics were studied in 28 healthy habitual cigarette smokers. Eight subjects received cotinine fumarate, 4 .mu.g base/kg per min i.v. for 60 min. Mean (.+-. SD) metabolic clearance was 60 .+-. 12 ml/min and mean renal clearance was 12 .+-. 5 ml/min, averaging 17% of total clearance. Steady-state volume of distribution was slightly greater than body wt (mean 88 .+-. 17 l). Terminal t1/2 [half-life] averaged 15.8 .+-. 4.0 h in these 8 subjects and 19.7 .+-. 6.5 h in another 12 subjects who abstained from smoking for 3 days. The effect of urinary acidification and alkalinization on renal clearance of cotinine during cigarette smoking was studied in another group of 8 subjects. Compared with baseline (mean urinary pH 5.8, renal clearance 12.3 .+-. 5.9 ml/min), renal clearance was increased about 50% by urinary acidification (pH 4.4, clearance 18.6 .+-. 10 ml/min), but it was not affected by alkalinization (pH 6.7, clearance 14.0 .+-. 10.4 ml/min). Infusion of cotinine to blood concentrations seen in moderately heavy smokers had no effect on heart rate, blood pressure or skin temperature, measures that are sensitive to effects of nicotine. No spontaneous subjective effects were reported. At levels to which cigarette smokers are generally exposed, cotinine evidently exerts no cardiovascular activity and weak, if any, psychologic activity.