Role of nicotine pharmacokinetics in nicotine addiction and nicotine replacement therapy: A review

Introduction
Smoking addiction is driven largely by nicotine pharmacokinetics, particularly the speed and efficiency with which nicotine reaches the brain.
This review examines how differences in nicotine absorption, distribution, metabolism, and elimination influence addiction and the effectiveness of nicotine replacement therapy (NRT).
The paper focuses on pharmacological mechanisms rather than social or behavioral factors.
Key Points
Rapid brain delivery: Inhaled nicotine from cigarettes reaches the brain within 10–20 seconds, producing strong reinforcement and high addiction potential.
Route of administration matters: Smoking delivers nicotine faster and at higher peak concentrations than oral, nasal, or transdermal NRT products.
Pharmacokinetic profiles: NRT products deliver nicotine more slowly and at lower peaks, resulting in less reinforcement but effective withdrawal relief.
Individual variability: Nicotine metabolism varies widely between individuals due to genetics, sex, ethnicity, liver function, and smoking behavior.
Tolerance and dependence: Repeated nicotine exposure leads to tolerance through receptor desensitization and upregulation of nicotinic acetylcholine receptors.
Combination NRT: Using multiple NRT forms (e.g., patch + gum or inhaler) can better mimic smoking nicotine levels and improve cessation outcomes.
Safety considerations: Nicotine itself is not the primary cause of smoking-related disease; most harm comes from toxic combustion products in tobacco smoke.
Conclusion
The addictive potential of smoking is closely linked to the rapid and efficient delivery of nicotine to the brain.
Differences in pharmacokinetics explain why NRT is less addictive than cigarettes yet effective for reducing withdrawal symptoms.
Optimizing NRT dosing, duration, and combination therapy may improve quit rates, especially for heavily dependent smokers

Le Houezec, Jacques. “Role of Nicotine Pharmacokinetics in Nicotine Addiction and Nicotine Replacement Therapy: A Review.” The International Journal of Tuberculosis and Lung Disease, vol. 7, no. 9, 2003, pp. 811–819.