Plasma Levels of Nicotine and Safety of Smokers Wearing Transdermal Delivery Systems During Multiple Simultaneous Intake of Nicotine and During Exercise

Abstract

Although transdermal nicotine patches have been studied extensively under recommended conditions, the present studies were designed to assess the nicotine plasma levels and the safety of transdermal nicotine patches in smokers undergoing situations suspected to result in increased nicotine plasma levels. The first study examined the effects of increasing nicotine intake through sequential administration of a nicotine patch (day 2), a patch followed by consumption of nicotine gum (day 3), and a patch followed by gum consumption and cigarette smoking (day 4). In this study, nicotine plasma levels increased transiently after the addition of each nicotine source. Mean areas under the concentration-time curves from 0 to 24 hours (AUC0-24) for nicotine were 453 +/- 120 ng.hr/mL (day 2), 489 +/- 143 ng.hr/mL (day 3), and 485 +/- 143 ng.hr/mL (day 4). The second study evaluated the effects of physical exercise on the kinetics and the safety of two different types of nicotine transdermal devices: Nicoderm and Habitrol. The mean delivered dose of nicotine was higher with Nicoderm compared with Habitrol, and the two products were not considered to be bioequivalent. During a 20-minute exercise period, nicotine plasma levels increased by 13 +/- 9% for Nicoderm and 30 +/- 20% for Habitrol. This increase in nicotine plasma levels was probably related to the exercise-induced increase in peripheral circulation at the patch site. Results from both studies indicate a clinically nonsignificant increase in blood pressure and heart rate after the administration of nicotine. After exercise, subjects taking Habitrol tended to have a higher incidence of adverse events compared with baseline values. Safety profiles remained acceptable in both studies despite the increases in nicotine plasma levels. It was concluded that both superimposed nicotine sources and physical exertion result in short-lived plasma nicotine elevations and temporarily increase nicotine pharmacodynamic parameters without increased risk to the volunteers.

FOXM1 Upregulation Is an Early Event in Human Squamous Cell Carcinoma and it Is Enhanced by Nicotine during Malignant Transformation

“…Nicorette, Nicotinell) contains between 2–4 mg nicotine and is expected to produce millimolar concentrations in the oral cavity. Some nicotine skin patches contain up to 21 mg nicotine (NicoDerm) which can deliver up to ∼3 mM/hr (500 ng.hr/ml) of plasma nicotine level [23] and is expected to produce much higher nicotine concentration locally on the skin. Although no evidence to date links nicotine exposure alone to human cancer, it has been previously shown that nicotine is co-carcinogenic with a tobacco smoke derivative benzo(a)pyrene in causing skin cancer in mice [24].…”

Green Tobacco Sickness in Children and Adolescents

“…6,17,18,20,21 Physical exercise and high ambient temperatures can increase absorption of nicotine, thereby increasing plasma nicotine concentrations by 30% to 45%. 22,23 In the United States, tobacco is usually harvested in late August or early September, when the ambient temperature is high. The combination of high ambient temperatures and hard physical labor shunts blood to the skin to help lower body temperature.…”

Smoking Cessation: Significance and Implications for Children

“…Plasma levels average between 10 and 20 ng/ml, i.e., in the range of trough levels seen during daily smoking of light to moderate smokers [51]. Note that even patches with the same nominal dose of nicotine differ significantly in their pharmacokinetic and pharmacodynamic characteristics during both acute dosing (24 h after first application) and steady state [53,54].…”