Abstract

The objectives of this study were to 1) quantitatively assess human exposure to various metabolites of nicotine, 2) examine the influence of inhalation vs. transdermal administration on the patterns of nicotine metabolism, and 3) assess the extent of recovery of nicotine as various metabolites in people whose systemic intake of nicotine has been measured. Twelve smokers were studied while smoking cigarettes and while receiving transdermal nicotine. Urinary excretion of nicotine and eight of its metabolites was measured under steady state conditions. The systemic intake of nicotine in these subjects was determined using plasma concentrations and intravenous clearance data, so the percentage of their daily dose of nicotine excreted as various metabolites could be computed. The major findings of the study are as follows: 1) a high percentage (averaging 88%) of a systemic dose of nicotine can be accounted for by measurement of nicotine and its metabolites; 2) the pattern of metabolism is generally similar when nicotine is inhaled or absorbed transdermally; 3) while there is considerable interindividual variability in the pattern of metabolism, the pattern is consistent for an individual; and 4) within individuals, the extent of conjugation of nicotine and cotinine is highly correlated, but neither is correlated with the extent of conjugation of 3'-hydroxycotinine. This suggests that similar enzymes are involved in the conjugation of nicotine and cotinine, and that a different enzyme may be involved in the conjugation of 3'-hydroxycotinine.