Absorption, Distribution, and Elimination of Nicotine

AuthorJames G. Wigmore
 2
Absorption, Distribution, and Elimination
of Nicotine
“There is good evidence that nicotine plays a role in tobacco dependence.
Consequently, it is important to understand the quantity and time course
of nicotine in the body. Following smoking, or an intravenous infusion,
nicotine distributes rapidly into tissues, after which it is eliminated with a
terminal half-life of about  hours.
—Jacob III et al, “Recent Studies of Nicotine
Metabolism in Humans” ()
The absorption, distribution, and elimination of a drug by the body is
called pharmacokinetics. Nicotine is a highly water-soluble drug similar
to alcohol but is also more fat (lipid) soluble than alcohol. The absorption,
distribution, and elimination patterns are a mixture of alcohol and tetra-
hydrocannabinol (THC) pharmacokinetics. As discussed in the f‌irst sec-
tion, nicotine is absorbed readily through the skin, unlike alcohol or THC,
which can cause poisoning when nicotine e-liquids are spilled on the skin.
When a person smokes, nicotine is distributed to the brain rapidly,
within a minute, causing a rapid rise in nicotine concentration. This leads
to a greater addiction in contrast to alcohol, which is more slowly distrib-
uted to the brain after ingestion due to its oral ingestion.
Nicotine concentration, like that of THC, decreases rapidly after
inhalation as the drug is distributed throughout the body by the blood.
After the initial rapid drop in blood nicotine concentration caused by
redistribution, nicotine is eliminated mainly by the liver at a half-life of
about  hours. This requires smokers to smoke numerous cigarettes to
maintain a blood nicotine level and prevent withdrawal symptoms.
 | Wigmore on Nicotine and Its Drug Delivery Systems
“Cigarette companies control the impact and delivery of nicotine in many
ways, including designing f‌ilters and selecting cigarette paper to maximize
the ingestion of nicotine, adding ammonia to make the cigarette taste less
harsh, and controlling the physical and chemical make-up of the tobacco
—Court-ordered Corrective Statements,
US v Philip Morris USA Inc, RICO decision ()
Nicotine absorption can occur through the oral cavity, lung, skin, eyes,
urinary bladder, and stomach. However, nicotine is poorly absorbed
through the stomach due to the acidity of the gastric f‌luids (). The
rate of nicotine absorption is based on pH. Cigarette smoke is mainly
acidic (pH -
tine rapidly approaches physiological pH of > in the lungs and is rapidly
absorbed (–). The absorption of nicotine from cigarette smoke is
similar to IV injection ().
The pH of pipe and cigar tobacco is typically > and so nicotine can
readily be absorbed through the oral cavity and does not need to be
inhaled into the lungs ().
One basic principle is that the faster a psychoactive drug is absorbed
the more addictive it is. For example, the absorption of nicotine is very
rapid when inhaled in cigarettes and vaping devices, but when nicotine
is absorbed slowly, such as dermally (nicotine patch), it becomes much
less addictive ().
Smokers tend to regulate their pung pattern to maintain a similar
blood nicotine concentration no matter what the nicotine concentration
of the tobacco they smoke (). One indicator of recent smoking is
the blood carbon monoxide concentration (COHb), as burning tobacco
produces this toxic gas (–). This indicator is of limited value in
e-cigarettes, which produce virtually no carbon monoxide (CO) gas in
their vapor.
Before laws banning smoking indoors and in numerous other public
spaces, it was virtually impossible for a non-smoking person to avoid
absorbing nicotine ().
Electronic cigarettes have been developed since the early cig-a-likes,
which were similar in size to cigarettes, to increase the absorption of
Absorption, Distribution, and Elimination of Nicotine | 
Reference Number: 
nicotine to the speed of regular cigarettes and thus increase its addict-
iveness (–). Tobacco and vaping companies adjusted the pH of
their products, in part by adding f‌lavors, in order to increase nicotine
absorption rate (–). Nicotine can also be absorbed if the e-liquid
is spilled on the skin ().
The dermal absorption of nicotine is employed in patches or transder-
mal nicotine systems, to allow smokers to avoid the worse symptoms of
nicotine withdrawal when quitting cigarettes or other tobacco products
(–). A slight increase in blood nicotine concentrations can occur
due to increased dermal blood f‌low during exercise ().
Reference Number: 20101
, .. “Facts About Nicotine Toxicity.Arhiv za higijenu rada i tok-
sikologiju, : –,  ( table,  references)
Abstract: Nicotine is an alkaloid obtained from the leaves of the tobacco
plant. It was f‌irst isolated in . Nicotine absorption can occur through
the oral cavity, lungs, skin, urinary bladder, and gastrointestinal tract.
Nicotine is absorbed poorly through the stomach, due in part to the acid-
ity of the gastric f‌luids. The respiratory absorption of nicotine is –%
and is the most rapid route of absorption. Nicotine is excreted through
the urine, feces, bile, saliva, gastric f‌luids, sweat, and breast milk.
Cigarette smoking is the major cause of chronic obstructive lung disease.
Nicotine, which is readily absorbed from the lung and distributed to tis-
sue, including bone marrow, increases the expression of the elastase gene,
leading to increased elastase protein concentration per cell, suggesting a
pathophysiologic mechanism for emphysema. Inhaled nicotine produces
a concentration-dependent cough and airway obstruction in healthy sub-
jects, probably because of stimulation of af‌ferent nerve endings in the bron-
chial mucosa and mediated through parasympathetic cholinergic pathways.
Reference Number: 20102
, ., . ,  . . “Pharmacokinetics and Metab-
olism of Nicotine.Pharmacological Reports: : –,  ( table,
 f‌igure,  references)
Abstract: The widespread use of cigarettes and other tobacco products is
mainly caused by addiction to nicotine. Pulmonary absorption of nicotine

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