Nicotine is a key component of tobacco and is involved in addiction and smoking behavior. It is metabolized primarily by the liver enzymes CYP2A6, UDP-glucuronosyltransferase (UGT), and flavin-containing monooxygenase (FMO). Nicotine metabolism is influenced by genetic, dietary, age, sex, hormone use, pregnancy, kidney disease, and other medications. Racial/ethnic differences in nicotine metabolism are likely due to genetic and environmental factors. Cotinine is the most widely used biomarker for nicotine intake, measured in blood, urine, saliva, hair, or nails. The optimal plasma cotinine cut-point to distinguish smokers from non-smokers in the US is 3 ng/ml, reflecting reduced secondhand smoke exposure and more light smoking. Nicotine is absorbed from tobacco and nicotine products, with absorption depending on pH. Flue-cured tobacco smoke is acidic, leading to minimal buccal absorption, while air-cured tobacco smoke is more alkaline, allowing significant nicotine absorption. Nicotine is rapidly absorbed through the lungs, reaching the brain within 10-20 seconds. Blood nicotine levels rise quickly during smoking, peaking at the end of smoking. Nicotine is distributed throughout the body, with high affinity for the liver, kidney, spleen, and lung. It is metabolized to cotinine, which is excreted in urine. Nicotine is also metabolized to other compounds, including nicotine N'-oxide, nicotine isomethonium ion, and glucuronides. Nicotine metabolism is influenced by various factors, including diet, meals, age, sex, hormone use, pregnancy, kidney disease, and medications. Cigarette smoking itself can affect nicotine metabolism, with some compounds in tobacco smoke inhibiting CYP2A6. Racial and ethnic differences in nicotine metabolism are observed, with blacks having slower metabolism than whites. Nicotine and cotinine metabolism are influenced by CYP2A6 activity, which can be assessed using the 3'-hydroxycotinine/cotinine ratio. This ratio is a useful marker for CYP2A6 activity and can predict response to pharmacotherapy. Renal excretion of nicotine and cotinine varies with urinary pH, with higher excretion in acidic urine. Cotinine is primarily excreted unchanged in urine, while nicotine is metabolized to various compounds. Renal clearance of nicotine and cotinine is reduced in kidney disease, leading to increased serum nicotine levels. Nicotine and cotinine blood levels during tobacco use and nicotine replacement therapy vary, with peak levels occurring after smoking a cigarette and trough levels during the day. Nicotine replacement therapies, such as nicotine gum, transdermal patches, and nasal spray, have different absorption rates and bioavailability. Nicotine is well absorbed through the skin, leading to occupational risks in tobacco harvesters. The metabolism of nicotine and cotinine is complex, with various pathways and enzymes involved.Nicotine is a key component of tobacco and is involved in addiction and smoking behavior. It is metabolized primarily by the liver enzymes CYP2A6, UDP-glucuronosyltransferase (UGT), and flavin-containing monooxygenase (FMO). Nicotine metabolism is influenced by genetic, dietary, age, sex, hormone use, pregnancy, kidney disease, and other medications. Racial/ethnic differences in nicotine metabolism are likely due to genetic and environmental factors. Cotinine is the most widely used biomarker for nicotine intake, measured in blood, urine, saliva, hair, or nails. The optimal plasma cotinine cut-point to distinguish smokers from non-smokers in the US is 3 ng/ml, reflecting reduced secondhand smoke exposure and more light smoking. Nicotine is absorbed from tobacco and nicotine products, with absorption depending on pH. Flue-cured tobacco smoke is acidic, leading to minimal buccal absorption, while air-cured tobacco smoke is more alkaline, allowing significant nicotine absorption. Nicotine is rapidly absorbed through the lungs, reaching the brain within 10-20 seconds. Blood nicotine levels rise quickly during smoking, peaking at the end of smoking. Nicotine is distributed throughout the body, with high affinity for the liver, kidney, spleen, and lung. It is metabolized to cotinine, which is excreted in urine. Nicotine is also metabolized to other compounds, including nicotine N'-oxide, nicotine isomethonium ion, and glucuronides. Nicotine metabolism is influenced by various factors, including diet, meals, age, sex, hormone use, pregnancy, kidney disease, and medications. Cigarette smoking itself can affect nicotine metabolism, with some compounds in tobacco smoke inhibiting CYP2A6. Racial and ethnic differences in nicotine metabolism are observed, with blacks having slower metabolism than whites. Nicotine and cotinine metabolism are influenced by CYP2A6 activity, which can be assessed using the 3'-hydroxycotinine/cotinine ratio. This ratio is a useful marker for CYP2A6 activity and can predict response to pharmacotherapy. Renal excretion of nicotine and cotinine varies with urinary pH, with higher excretion in acidic urine. Cotinine is primarily excreted unchanged in urine, while nicotine is metabolized to various compounds. Renal clearance of nicotine and cotinine is reduced in kidney disease, leading to increased serum nicotine levels. Nicotine and cotinine blood levels during tobacco use and nicotine replacement therapy vary, with peak levels occurring after smoking a cigarette and trough levels during the day. Nicotine replacement therapies, such as nicotine gum, transdermal patches, and nasal spray, have different absorption rates and bioavailability. Nicotine is well absorbed through the skin, leading to occupational risks in tobacco harvesters. The metabolism of nicotine and cotinine is complex, with various pathways and enzymes involved.