Clinical Pharmacokinetics

, Volume 40, Issue 9, pp 661–684 | Cite as

The Nicotine Inhaler

Clinical Pharmacokinetics and Comparison with Other Nicotine Treatments
  • Nina G. Schneider
  • Richard E. Olmstead
  • Mikael A. Franzon
  • Erik Lunell
Review Articles Drug Disposition

Abstract

Nicotine inhaled in smoke is the most rapid form of delivery of the drug. With smoking, arterial boli and high venous blood nicotine concentrations are produced within seconds and minutes, respectively. The potency of nicotine as the primary reinforcement in tobacco addiction is attributed to this rapid rate of delivery. By design, nicotine treatments reduce the rate and extent of drug delivery for weaning from nicotine during smoking cessation. Theoretically, they prevent relapse by reducing withdrawal and craving associated with the abrupt cessation of cigarettes.

The nicotine inhaler treats the complexity of smoking through weaning both from the drug and from the sensory/ritual components associated with smoking. The inhaler is ‘puffed’ but not lit and there is considerable ‘puffing’ required to achieve slower rising and lower nicotine concentrations. These factors allow it to be used as a nicotine reduction treatment.

One inhaler contains 10mg of nicotine (and 1mg of menthol) of which 4mg of nicotine can be extracted and 2mg are systemically available. Shallow or deep ‘puffing’ results in similar nicotine absorption. Nicotine is delivered mainly to the oral cavity, throat and upper respiratory tract with a minor fraction reaching the lungs. This was confirmed with positron emission tomography and by assessment of arterial concentrations. A single inhaler can be used for one 20-minute period of continuous puffing or periodic use of up to 400 puffs per inhaler.

With controlled puffing in laboratory testing, venous plasma nicotine concentrations from a single inhaler puffed 80 times over 20 minutes averaged 8.1 μg/L at 30 minutes. Lower concentrations of 6.4 to 6.9 μg/L have been reported for self-administration under clinical conditions. The time to peak plasma concentrations varies but is always significantly longer than with cigarette delivery. Estimates of nicotine intake from cotinine concentrations were higher than expected (60 to 70% of baseline smoking concentrations). This elevation may be due to the swallowing of nicotine and subsequent first-pass biotransformation to cotinine. In general, venous blood nicotine concentrations are considerably lower than with smoking and are within the range observed for other nicotine reduction therapies.

Efficacy trials show consistent superiority of the inhaler over placebo. Despite the ‘cigarette-like’ appearance of the inhaler and the associated sensory/ritual elements, little treatment dependence or abuse has been reported. This is attributed to the slow rise time and low nicotine blood concentrations. The inhaler is a valuable addition to treatment of tobacco dependence and can be used alone or with other treatments.

Keywords

Nicotine Cotinine Harm Reduction Nicotine Patch Treatment Dependence 

Notes

Acknowledgements

Drs Schneider and Olmstead were funded by the first author’s VA Merit Review and NIDA Grant #DA11398. Special thanks to Shilpan Patel M.A., and Regina Harris for help in preparing the manuscript.

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Copyright information

© Adis International Limited 2001

Authors and Affiliations

  • Nina G. Schneider
    • 1
    • 2
  • Richard E. Olmstead
    • 1
    • 2
  • Mikael A. Franzon
    • 3
  • Erik Lunell
    • 4
  1. 1.University of California-Los Angeles, School of MedicineLos AngelesUSA
  2. 2.Nicotine Research UnitVA-Greater Los Angeles Healthcare SystemWest Los AngelesUSA
  3. 3.Pharmacia Consumer HealthcareBridgewaterUSA
  4. 4.Department of Clinical PharmacologyUniversity HospitalLundSweden

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