Kinetics of nicotine

An average cigarette delivers 10–30 μg of nicotine per kg of body weight in adults (68kg). An average smoker (smoking 17 cigarettes per day) absorbs about 20 mg or 300 µg per kg daily, resulting in 10–50 ng/ml peak plasma levels, while peak arterial levels can reach 100 ng/ml and reach the brain in 7-10 s, allowing the smoker to titrate nicotine dose and effect on a puff-by-puff basis to optimize the drug experience.

Blood nicotine levels peak at the end of smoking a cigarette and decline rapidly over the next 20 min due to distribution to all body tissues, with a volume of distribution averaging 2.6 times body weight. In the blood, at pH 7.4, nicotine is 31% non-ionized, with <5% binding to plasma proteins. The highest tissue affinity for nicotine is in liver, kidney, spleen, and lungs, and the lowest in adipose tissue. Nicotine easily crosses the placenta, entering fetal blood and amniotic fluid, and is distributed in breast milk with a milk-to-plasma ratio of 2.9 (the high-lipid-containing, more acidic milk causing the 3fold higher concentration).

Average elimination half-life for plasma nicotine is 2 h (clearance varying from < 1% in alkaline urine to >20% in acidic urine). Overnight abstinence leads to 4-5 ng/ml in the morning. Women metabolize nicotine 13% and cotinine 26% more rapidly than men, with oral contraceptives causing a 30/33% increase of nicotine/cotinine metabolism. In pregnancy metabolism of nicotine/cotinine is accelerated by 60/140%.

Oral nicotine is metabolized mainly to cotinine in the liver before reaching the arterial blood. Only about 30% of orally administered nicotine can be expected to reach the circulation.

Source: Matta et al. Psychopharmacology (2007) 190:269–319

Nicotine exposure during second-hand smoking: http://ajph.aphapublications.org/cgi/content/full/98/4/672