Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2016 Publisher: GlaxoSmithKline Consumer Healthcare (UK) Trading Limited, 980 Great West Road, Brentford, Middlesex, TW8 9GS, United Kingdom
Pharmacotherapeutic group: Drugs used in nicotine dependence
ATC Code: N07BA01
Nicotine, the primary alkaloid in tobacco products and a naturally occurring autonomous substance, is a nicotine receptor agonist in the peripheral and central nervous systems and has pronounced CNS and cardiovascular effects. On consumption of tobacco products, nicotine has proven to be addictive, resulting in craving and other withdrawal symptoms when administration is stopped. This craving and these withdrawal symptoms include a strong urge to smoke, dysphoria, insomnia, irritability, frustration or anger, anxiety, concentration difficulties, agitation and increased appetite or weight gain. The lozenge replaces part of the nicotine that would have been administrated via tobacco and reduces the intensity of the withdrawal symptoms and smoking urge.
The absorbed amount of nicotine depends on the amount released into the mouth and absorbed through the buccal mucosa.
The main part of nicotine in Nicotinell Mint 1 mg lozenge is absorbed through the buccal mucosa. A proportion, by the swallowing of nicotine-containing saliva, reaches the stomach and intestine where it is inactivated. Due to the first-pass effect in the liver, the systemic bioavailability of nicotine is low. Consequently, in the treatment with Nicotinell Mint 1 mg lozenge the high and quick systemic nicotine concentration, as seen when smoking, is rarely obtained.
Distribution volume after intravenous administration of nicotine is approximately 2-3 1/kg and the half-life is 2 hours. Nicotine is metabolised principally in the liver and the plasma clearance is approximately 1.2 l/min; nicotine also metabolises in the kidney and lungs. Nicotine crosses the blood-brain barrier.
More than 20 metabolites have been identified, all believed to be less active than nicotine. The main metabolite is cotinine which has a half-life of 15-20 hours and with approximately 10 times higher plasma concentration than nicotine. Nicotine’s plasma-protein binding is less than 5%. Changes in nicotine binding from the use of concomitant medicinal products or due to altered disease state are not expected to have significant effect on nicotine kinetics. The main metabolite in urine is cotinine (15% of the dose) and trans-3-hydroxy cotinine (45% of the dose).
About 10% of the nicotine is excreted unchanged. Up to 30% may be excreted with urine in increased diuresis and the acidity under pH 5.
The peak value for the plasma concentration of Nicotinell Mint 1 mg lozenge after a single dose is approximately 4 ng per ml and the maximal concentration at steady state is approximately 10.6 ng per ml (average plasma concentration of nicotine after smoking one cigarette is 15-30 ng per ml). Peak plasma concentration is reached after about 45 minutes following sucking of a single lozenge and after about 30 minutes at steady state.
Nicotine was positive in some in vitro genotoxicity tests but there are also negative results with the same test systems. Nicotine was negative in standard in-vivo tests.
Animal experiments have shown that nicotine induces post-implantation loss and reduces the growth of foetuses.
The results of carcinogenicity assays did not provide any clear evidence of a tumorigenic effect of nicotine.
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