Detection of Nornicotine in Human Urine after Infusion of Nicotine

Abstract

The role of oxidative N-dealkylation as a pathway of the human metabolism of nicotine has been investigated after intravenous infusion of nicotine. Nornicotine has been found in the urine presenting evidence for the existence of this metabolic step. But, only less than 1% of the administered dose of nicotine is excreted as nornicotine possibly indicating rapid further metabolism. Oxidative N-dealkylation is a major pathway in drug metabolism (Williams, 1971). Nornicotine would be the product of nicotine by this route (Papadopoulos and Kintzios, 1963, McKennis, Schwartz, and Bowman, 1964). After intraarterial application of nicotine, 8.9% of the administered dose were found in the urine of rats as nornicotine by Kyerematen et al. (1987). Nornicotine was also found in recent smoker studies by Neurath et al. (1988), but the nornico-tine was not in excess of 1.9%, 1.7%, and 1.4% respectively of the excreted sum of the total nicotine metabolites. Similar results have recently been reported (Zhang et al., 1990). As nornicotine occurs in minor and varying concentrations in most of the tobaccos (Kuhn, 1964), its occurrence in the urine of smokers does not prove its formation in the human metabolism: It may be directly absorbed by the smoker and pass unchanged to the urine.