Respiratory retention of nicotine and urinary excretion of nicotine and its five major metabolites in adult male smokers

Urinary excretion of nicotine and its five major metabolites (nicotine-N-glucuronide, cotinine, cotinine-N-glucuronide, trans-3'-hydroxycotinine, and trans-3'-hydroxycotinine-O-glucuronide), expressed as nicotine equivalents (NE), has been used as a biomarker of smoking-related nicotine exposure. In this open-label, single center study, we investigated the relationship between nicotine retention from smoking and urinary excretion of NE in adult smokers. After a 4-day washout period, 16 adult male smokers smoked 6 cigarettes per day for four consecutive days according to three predefined smoking patterns: no inhalation (Pattern A), normal inhalation (Pattern B), and deep inhalation (Pattern C). The amount of nicotine retained in the respiratory tract during smoking was estimated from the difference between the amounts of nicotine delivered and exhaled. The daily excretion of urinary NE was measured in 24h urine samples by LC-MS/MS. The mean (+/-S.D.) amount of nicotine retained was 0.126+/-0.167, 0.960+/-0.214, and 1.070+/-0.223mg/cig for Patterns A, B, and C, respectively. The mean (+/-S.D.) relative retention (the amount retained relative to the amount delivered) was 11.2+/-14.7%, 98.0+/-1.6%, and 99.6+/-0.3% for Patterns A, B, and C, respectively. On the fourth day of smoking, an average of 86+/-20% of the total daily amount of retained nicotine was recovered as NE in 24h urine. Nicotine equivalents was treated as a single component and the data was described by a first-order elimination pharmacokinetic model which assumed instantaneous input and distribution. Based on this model, the elimination half-life of NE was 19.4+/-2.6h, and the NE excretion had reached approximately 96% of the steady state levels by Day 4. Our results suggest that most of the nicotine inhaled from a cigarette is retained (> or =98%) in the lung, and at steady state, daily urine NE excretion reflects approximately 90% of the retained nicotine dose from cigarette smoking.