ADMET-Absorption, Distribution, Metabolism, Excretion, and Toxicity

StatusFDA approved
AdministrationSmoked (as smoking tobacco, mapacho, etc.), insufflated (as tobacco snuff or nicotine nasal spray), chewed (as nicotine gum, tobacco gum or chewing tobacco), transdermal (as nicotine patch, nicogel or topical tobacco paste), intrabuccal (as dipping tobacco, snus, dissolvable tobacco or creamy snuff), intravenously (as NicVAX)[clarification needed], vaporized (as electronic cigarette, etc.), directly inhaled (as nicotine inhaler), oral (as nicotini)
PharmacologyNicotine, the primary alkaloid in tobacco products binds stereo-selectively to nicotinic-cholinergic receptors on autonomic ganglia, the adrenal medulla, neuromuscular junctions and in the brain. Nicotine exerts two effects, a stimulant effect exerted at the locus ceruleus and a reward effect in the limbic system.

Absorption_value100.0
Absorption (description)As nicotine enters the body, it is distributed quickly through the bloodstream and can cross the blood-brain barrier. On average it takes about seven seconds for the substance to reach the brain when inhaled.
Caco_2-4.71
Bioavailability30.0

MetabollsmNicotine is metabolized in the liver by cytochrome P450 enzymes (mostly CYP2A6, and also by CYP2B6). A major metabolite is cotinine. Other primary metabolites include nicotine N'-oxide, nornicotine, nicotine isomethonium ion, 2-hydroxynicotine and nicotine glucuronide.
Half lifeAfter inhalation or parenteral administration, plasma half-life, nicotine 0.5 to 2 h, cotinine 6 to 16 h (mean 11).

ToxicityThe LD50 of nicotine is 50 mg/kg for rats and 3 mg/kg for mice. 40–60 mg (0.5-1.0 mg/kg) can be a lethal dosage for adult humans.
LD50 (rat)LD50=50 mg/kg
LD50 (mouse)LD50= 24 mg/kg