Pharmacotherapeutic Group: Drug used in nicotine dependence. ATC Code: N07BA01.
Pharmacology: Pharmacodynamics: Abruptly cessation of tobacco-containing products following a prolonged period of daily use results in a characteristic withdrawal syndrome that includes ≥4 of the following: Dysphoria or depressed mood; insomnia; irritability, frustration or anger; anxiety; difficulty concentrating, restlessness or impatience; decreased heart rate; and increased appetite or weight gain. Nicotine craving, which is recognized as a clinically relevant symptom, is also an important element in nicotine withdrawal.
Clinical studies have shown that nicotine replacement products can help smokers abstain from smoking.
Patch treatment mimics the fluctuations of nicotine over the day in smokers, with no nicotine administration during sleep. Daytime nicotine patch treatment does not give the nicotine induced sleep disturbances seen with nicotine administration during sleep.
Pharmacokinetics: All patches are labelled by the average amount of nicotine absorbed by the average patient over 16 hours.
Representative mean values of the Cmax for the patches are presented in the table as follows. (See Table 1).
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The calculated peak plasma levels are in the same range as true measured peak plasma concentration: 11 ng/mL for the 10 mg patch and 24.2 ng/mL for the 25 mg patch. Interpolation yields a peak plasma concentration of 15.4 ng/mL for the 15 mg patch.
The maximum level of plasma concentration after administration is reached after approximately 9 hours (tmax). The plasma peak is in the afternoon/evening when the risk of relapse is highest.
The volume of distribution of nicotine is about 2 to 3 L/kg and the half-life is approximately 3 hours. The major eliminating organ is the liver, and average plasma clearance is about 70 L/hour. The kidney and lung also metabolizes nicotine. More than 20 metabolites of nicotine have been identified, all of which are believed to be less active than the parent compound.
Plasma protein-binding of nicotine is less than 5%. Therefore, changes in nicotine binding from the use of concomitant drugs or alterations of plasma proteins by disease states would not be expected to have significant effects on nicotine kinetics.
The primary metabolite of nicotine in plasma, cotinine, has a half-life of 15 to 20 hours and concentrations that exceed nicotine by 10-fold.
The primary urinary metabolites are cotinine (10-12% of the dose) and trans-3-hydroxy-cotinine (28-37% of the dose). About 10-15% of nicotine is excreted unchanged in the urine.
Progressive severity of renal impairment is associated with decreased total clearance of nicotine. Raised nicotine levels have been seen in smoking patients undergoing hemodialysis.
The pharmacokinetics of nicotine is unaffected in cirrhotic patients with mild liver impairment (Child-Pugh score 5) and nicotine clearance is decreased by about 40-50% in cirrhotic patients with moderate liver impairment (Child-Pugh score 7).
A minor reduction in total clearance of nicotine has been demonstrated in healthy elderly patients, however, not justifying adjustment of dosage.
Plasma nicotine concentrations show dose proportionality for the three patch doses.