+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Sources of variability in nicotine and cotinine levels with use of nicotine nasal spray, transdermal nicotine, and cigarette smoking



Sources of variability in nicotine and cotinine levels with use of nicotine nasal spray, transdermal nicotine, and cigarette smoking



British Journal of Clinical Pharmacology 43(3): 259-267



Aims: Nicotine nasal spray and transdermal nicotine are effective aids to smoking cessation, and are being evaluated for treatment of other medical diseases. Wide variation in levels of nicotine and its metabolite, cotinine, have been observed with such therapies. This study aimed primarily to assess sources of individual variability in nicotine and metabolite plasma levels from these dosing systems and from cigarette smoking. Methods: Twelve cigarette smokers, studied on a clinical research ward, received four treatments of 5 days duration each, including (1) cigarette smoking, 16 cigarettes/day; (2) transdermal nicotine, 15 mg/day; (3) nicotine nasal spray, 24-1 mg doses/day; (4) placebo nicotine nasal spray, 24 doses/day. On a different occasion, the disposition kinetics of nicotine and cotinine were determined via infusion of deuterium-labeled nicotine and cotinine. Plasma levels of nicotine, cotinine, and 3'-hydroxycotinine and daily intake of nicotine during various treatments were examined, as well as pharmacokinetic factors that determined plasma nicotine and cotinine levels. Results: There was considerable individual variation in plasma nicotine and cotinine levels and in the daily dose of nicotine absorbed from various delivery systems, with most variability with nicotine nasal spray (fivefold) and least for transdermal nicotine (two-to threefold). Plasma nicotine levels were determined most strongly by nicotine clearance. Cotinine levels were determined most strongly by dose of nicotine and, to a lesser extent, the clearance of cotinine and fractional conversion of nicotine to cotinine. Conclusions: Plasma levels of nicotine and cotinine produced by nicotine therapies are highly variable, due to both wide variability in individual pharmacokinetics and in dose delivery from the products. To compensate for individual differences in clearance, individualization of nicotine dosing based on therapeutic drug monitoring with comparison to nicotine or cotinine levels during cigarette smoking prior to treatment may be necessary to optimize nicotine therapy. This study also validates a recently proposed method for estimating absolute bioavailability of a drug using drug and metabolite pharmacokinetic data, and presents novel data on plasma levels of the metabolite trans-3'-hydroxycotinine in people.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 009437395

Download citation: RISBibTeXText

PMID: 9088580

DOI: 10.1111/j.1365-2125.1997.00566.x


Related references

Comparison of plasma nicotine concentrations for nicotine transdermal system nts cigarette smoking and nicotine polacrilex nicotine gum. Clinical Pharmacology & Therapeutics 51(2): 129, 1992

Determinants of plasma concentrations of nicotine and cotinine during cigarette smoking and transdermal nicotine treatment. European Journal Of Clinical Pharmacology. 51(5): 407-414, 1997

Nicotine and cotinine replacement when nicotine nasal spray is used to quit smoking. Psychopharmacology. 137(4): 345-350, E, 1998

Effects of a nicotine-enriched cigarette on nicotine titration, daily cigarette consumption, and levels of carbon monoxide, cotinine, and nicotine. Psychopharmacology 77(2): 164-167, 1982

Nicotine, cotinine, withdrawal, and craving patterns during smoking and nicotine nasal spray use: results from a pilot study with African American men. Nicotine & Tobacco Research 9(1): 65-82, 2007

Arteriovenous differences in plasma concentration of nicotine and catecholamines and related cardiovascular effects after smoking, nicotine nasal spray, and intravenous nicotine. Clinical Pharmacology and Therapeutics 62(4): 453-463, 1997

Information from your family doctor. Using the nicotine patch, nicotine gum, nicotine nasal spray or nicotine inhaler. American Family Physician 63(11): 2251-2252, 2001

Effects of nicotine patch or nasal spray on nicotine and cotinine concentrations in pregnant smokers. Journal of Maternal-Fetal and Neonatal Medicine 22(9): 751-758, 2009

Determinants of plasma levels of nicotine and cotinine during transdermal nicotine treatment. Clinical Pharmacology & Therapeutics 59(2): 209, 1996

Integrating transdermal nicotine therapy into nicotine fading treatments: Effects on salivary cotinine levels. Psychology of Addictive Behaviors 13(4): 279-283, 1999

High dose transdermal nicotine therapy for heavy smokers: Safety, tolerability and measurement of nicotine and cotinine levels. Psychopharmacology 122(3): 215-222, 1995

Nicotine metabolic profile in man: comparison of cigarette smoking and transdermal nicotine. Journal of Pharmacology and Experimental Therapeutics 268(1): 296-303, 1994

Suppression of nicotine intake during ad libitum cigarette smoking by high-dose transdermal nicotine. Journal of Pharmacology and Experimental Therapeutics 287(3): 958-962, 1998

Nicotine effects on eicosanoid formation and hemostatic function: Comparison of transdermal nicotine and cigarette smoking. Journal of the American College of Cardiology 22(4): 1159-1167, 1993

Comparison of the nicotine pharmacokinetics of Nicoderm (nicotine transdermal system) and half-hourly cigarette smoking. Journal of Clinical Pharmacology 35(10): 985-989, 1995