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: https://ajph.aphapublications.org/doi/abs/10.2105/AJPH.2007.126631 http://ajph.aphapublications.org/cgi/content/full/98/4/672
Nicotine uptake via skin and clothes: https://onlinelibrary.wiley.com/doi/full/10.1111/ina.12327 http://onlinelibrary.wiley.com/doi/10.1111/ina.12327/full