Cotinine primary metabolites

Absorption occurs through the respiratory tract, orai membranes, and skin (Taylor 1996). Absorption from the stomach is iimited, uniess the acidity is reduced, because nicotine is a strong base. Between 80 and 90% of nicotine is metabolized, mainly in the liver but also the kidneys and lungs. Cotinine is the primary metabolite of nicotine, and the half-life of nicotine is about 2 hours. Elimination occurs by the kidneys, but it is also present in the breast milk of lactating women. 

Nicotine is extensively metabolized to a nnmber of metabolites (Fig. 3) by the liver. Six primary metabolites of nicotine have been identified. Qnantitatively, the most important metabolite of nicotine in most mammalian species is the lactam derivative, cotinine. In humans, about 70-80% of nicotine is converted to cotinine. This transformation involves two steps. The first is mediated primarily by CYP2A6 to produce nicotine-A -iminium ion, which is in equilibrium with 5 -hydroxynicotine. The second step is catalyzed by a cytoplasmic aldehyde oxidase. Nicotine iminiiim ion has received considerable interest since it is an alkylating agent and, as such, could play a role in the pharmacology of nicotine (Shigenaga etal. 1988). 

Although on average about 70-80% of nicotine is metabolized via the cotinine pathway in humans, only 10-15% of nicotine absorbed by smokers appears in the urine as unchanged cotinine (Benowitz et al. 1994). Six primary metabolites of cotinine have been reported in humans 3 -hydroxycotinine (McKennis et al. 1963 Neurath et al. 1987), 5 -hydroxycotinine (also called allohydroxycotinine) (Neurath 1994), which exists in tautomeric equilibrium with the open chain derivative... 

Nicotine has been measured in the hair of workers exposed to environmental tobacco smoke (ETS), and a significantly greater level in the level of nicotine in the hair of non-smokers exposed to ETS in the workplace has been observed. However, cotinine (the primary metabolite of nicotine) is a preferred marker of exposure to ETS, particularly as measured in blood, saliva or urine, because up to 80% of a dose of nicotine is metabolically converted to cotinine. Cotinine metabolite has a half-life of 15-17 h, while nicotine has a much shorter half-life and has different clearance rates in smokers and nonsmokers. 

A compilation of studies describing the effects of nicotine (1) in biological systems is available [15], Specific examples of the effects of nicotine and its primary metabolite, cotinine (5), are described below. 

Nicotine produced teratogenic effects in test animals, causing postimplantation mortality, fetal death, and developmental abnormalities. Nicotine and its primary metabolite cotinine exhibited teratogenic potential with Xenopus frog embryo teratogenesis assay (Dowson et al. 1988). 

Refers to cotinine, the primary plasma metabolite of nicotine. 

Nicotine forms a number of metabolites in the body, mainly in the liver. Approximate 75% of nicotine is oxidized to cotinine, which is the primary nicotine metabolite. Cotinine can be measured in the blood, urine, and saliva and this is used as a measure of nicotine exposure in tobacco users and in those exposed to secondhand smoke. The oxidation of nicotine also produces nicotinic acid. Nicotinic acid is vitamin B3 and has the common name niacin. Niacin deficiency results in a disease called pellagra, which is found in certain malnourished populations. Pellagras symptoms include dermatitis, diarrhea, sensitivity to light, and dementia. 

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