Nicotine Transdermal Systems Research Articles

Comparison of the Pharmacokinetics of Two Nicotine Transdermal Systems: Nicoderm and Habitrol

This randomized, crossover study compared the nicotine and cotinine pharmacokinetic parameters and plasma concentration profiles of two different nicotine transdermal products: Nicoderm (Alza, Palo Alto, CA; and Marion Merrell Dow, Kansas City, MO) and Habitrol (Basel Pharmaceuticals, Summit, NJ). The two treatments were randomly assigned to each of 24 male smokers and worn for 24 hours each day for 5 days, with a 6-day washout between treatments. Plasma nicotine and cotinine concentrations were measured on day 1 and day 5 of each treatment. Mean delivered dose differed significantly between products, and the two products were not bioequivalent. The Nicoderm system provided higher mean plasma nicotine concentrations, particularly during the first 8 hours after system application. The mean steady state Cmax, AUC, and degree of fluctuation (DF) values were significantly greater for the Nicoderm system than for Habitrol. The mean nicotine tmax value for the Nicoderm system was significantly shorter (P < .001) than that for Habitrol (2.7 versus 8.6 hours). Steady state cotinine AUC values and plasma concentrations were significantly lower for Habitrol than for the Nicoderm system. The incidence of adverse events was similar for both products.

Absorption and Adverse Effects following Topical and Oral Administration of Three Transdermal Nicotine Products to Dogs

To evaluate potential adverse effects from inadvertent exposure to a nicotine transdermal system or “patch”, three marketed products were administered topically and orally to dogs: Nicoderm (nicotine transdermal system), with a drug reservoir and a rate‐controlling membrane; Nicotinell, with a nicotine solution dispersed in a cotton gauze pad between layers of adhesive; and Niconil, with a nicotine gel matrix. Nicotine doses during topical administration ranged from 1 to 2 mg/kg/24 h for all three products, with plasma nicotine concentrations as high as 43 ng/mL. Two of the 12 topical exposures (with Nicotinell and Niconil) were associated with clinical signs (excess salivation or emesis). The oral doses from the products ranged from 2.8 mg/kg (one patch) to 13.4 mg/kg (two patches) over 25‐57 h, with mean maximal plasma levels of 73 ng/mL for two patches (mean maximal level 36 ng/mL). These doses are 2–9‐fold higher than oral doses reported to produce severe toxicity in children and, at the highest dose, within the known lethal range for dogs. Oral dosing of Nicotinell and Niconil (two patches per dog) produced vomiting in 2 of 12 exposures. No clinical signs were observed with either topical or oral dosing of Nicoderm. These data suggest that nicotine toxicity in dogs from nicotine transdermal patches may not be as severe as might be anticipated based on nicotine content alone.

Comparative Efficacy and Tolerability of Nicotine Replacement Therapies

While tobacco use has declined in many industrialised nations, it remains a leading cause of preventable illness and death worldwide. Nicotine replacement therapy can play a role in assisting tobacco users to terminate their addiction. To this end, 4 different nicotine replacement therapies have been developed: (i) nicotine chewing gum (polacrilex); (ii) transdermal nicotine systems (patch); (iii) nicotine nasal spray; and (iv) nicotine inhalers.

Treatment of nicotine dependence

Drug and nondrug interventions used in treating nicotine dependence are reviewed. Tobacco use is the leading preventable cause of death in the United States. Risks of smoking-related disease and death decline sharply when smokers quit, but 26% of Americans continue to smoke. Most smokers find it extremely difficult to quit smoking because of their nicotine addiction. Nonpharmacologic interventions used to promote smoking cessation include behavioral therapy, setting a specific date for quitting, receiving advice to quit from a health care professional, follow-up visits to review progress, self-help approaches, group counseling, filtration devices, hypnosis, and acupuncture. The efficacy of these approaches ranges from substantial to almost nil. The only pharmacologic agent with FDA-approved labeling for use in smoking-cessation therapy is nicotine. When used in conjunction with appropriate nonpharmacologic interventions, nicotine-replacement therapy roughly doubles the rate of quitting obtained with placebo. Nicotine-replacement therapies consist of nicotine transdermal (patch) systems and nicotine chewing gum. The nicotine patch is the first-line replacement therapy because it is effective when accompanied by only minimal (as opposed to more intensive) nonpharmacologic interventions and because it is easier to use and comply with than gum. Clonidine, antidepressants, and buspirone require further study to determine what role, if any, they should play in the treatment of nicotine dependence. The stages of smoking cessation are precontemplation, contemplation, action, and maintenance; interventions are selected on the basis of the stage the smoker is in. Nicotine dependence is difficult to treat, but there are aids that boost a smoker's chances of quitting. Nicotine patches and chewing gum offer the most effective pharmacologic options, especially when combined with behavioral interventions and counseling.

Cholesterol Changes in Smoking Cessation Using the Transdermal Nicotine System

Background. Cigarette smoking is a well-known major risk factor in coronary heart disease. Smoking cessation results in a positive change in atherogenic factors. High-density lipoprotein cholesterol has been observed as increasing with smoking cessation. Since the use of nicotine transdermal replacement has become so widespread, this study examined the effect, if any, of the transdermal nicotine system on selected cardiovascular parameters in patients who were abstinent from cigarette smoking, and possible dose effect. Methods. Eight cardiovascular outcome measures were evaluated at baseline and Week 6 in both abstinent and nonabstinent patients randomized to four treatment groups; transdermal nicotine system 7 mg, 14 mg, and 21 mg per day, and placebos. Results. In abstinent patients, systolic blood pressure and heart rate decreased from baseline (while still smoking, before the start of the study) to the end of transdermal treatment, while weight increased. Similarly, HDL increased while LDL decreased and triglycerides increased. In nonabstinent patients, weight also increased from baseline to Week 6 while heart rate decreased. No other variables showed significant change. In abstinent patients, effect of nicotine dosage was observed with greater weight gain in placebo than 21 mg TTS patients and greater decrease in heart rate in placebo than 21 mg TTS patients. Conclusions. In summary, the abstinent patients showed a positive effect of smoking cessation on cardiovascular risk factors even while using the transdermal nicotine system. These findings are favorable since the transdermal nicotine system has become a useful method of nicotine replacement in smoking cessation programs.

Development of a new nicotine transdermal delivery system: in vitro kinetics studies and clinical pharmacokinetic evaluations in two ethnic groups

Nicotine transdermal delivery systems (nicotine-TDSs) have provided effective assistance to smokers in smoking cessation with minimal occurrence of withdrawal symptoms. However, substantial skin reactions have been reported with the four nicotine-TDSs marketed recently. To reduce the skin reactions, a new type of nicotine-TDS has been recently developed. In vitro skin permeation studies demonstrated that this nicotine-TDS yields a constant skin permeation profile with a permeation rate of 0.068 ( ± 0.003 ) mg/cm 2/h across human cadaver skin and 0.059 ( ± 0.014 ) mg/cm 2/h across hairless rat skin, which are comparable to the steady-state permeation rates attained by Habitrol ™ and Nicoderm ® systems. The clinical pharmacokinetic evaluations in two ethnic groups of smokers indicated that a steady-state nicotine plasma level has been maintained throughout the course of 24-h topical application. While a higher daily dosage of nicotine has been delivered transdermally to Taiwanese smokers, from all three patch sizes, than to American smokers, no clear demographic effect was detected in most pharmacokinetic parameters between these ethnic groups, even after taking the difference in subjects body weight into consideration.

Transdermal nicotine system for smoking cessation

LetterMarch 1, 1993Transdermal nicotine system for smoking cessationRowen K. Zetterman, MDRowen K. Zetterman, MDUniversity of Nebraska Medical Center, Omaha, Nebraska (R.K.Z.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-1993-118-2-062 SectionsAboutFull Text ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinkedInRedditEmail To the EditorAn article published by the Transdermal Nicotine Study Group (Transdermal Nicotine System for Smoking Cessation) was abstracted and reviewed by ACP Journal Club (1). Because one of the authors is a friend, my attention was drawn to the comments of the reviewer. When this study was published, the authors carefully disclosed their financial relationships to the sponsoring pharmaceutical company. In his discussion the reviewer stated, ". . . 10 of the authors are identified as employees and stockholders . . . and 11 others have received honoraria and consultant fees from the maker . . ." He added, ...References1 Bronson DL. Commentary on "Transdermal Nicotine System for Smoking Cessation." ACP J Club. 1992 May-June:80 (Ann Intern Med. vol 116, suppl 3). Comment on: Transdermal Nicotine Study Group. Transdermal nicotine for smoking cessation. Six-month results from two multicenter controlled clinical trials. JAMA. 1991;266:3133-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Nebraska Medical Center, Omaha, Nebraska (R.K.Z.) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails March 1, 1993Volume 118, Issue 2Page: 62KeywordsConflicts of interestDisclosureNicotine ePublished: 9 March 2020 Issue Published: March 1, 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.Loading ...

Single‐ and Multiple‐Dose Pharmacokinetics of Nicoderm® (Nicotine Transdermal System)

The pharmacokinetics and tolerability of single and multiple applications of Nicotine Transdermal Systems (NTS), designed to deliver 14 mg of nicotine per 24 hours, were investigated in 20 healthy adult male smokers. After a single application, mean Cmax and tmax for plasma nicotine were 12.2 ng/mL and 4.4 hours, respectively. Plasma nicotine concentrations rose rapidly and then remained steady between 12 and 24 hours after application. The apparent nicotine half-life (t1/2) after system removal was 3.2 hours. Steady state was attained by the second day of multiple application, and mean steady-state nicotine Cavg was 25% higher on day 5 compared with the first NTS application. Steady-state plasma cotinine was reached by the fourth day of multiple application and, as with nicotine, Cavg and Cmax increased, tmax decreased, and t1/2 did not change compared with single application. The mean ratios of cotinine-to-nicotine area under the curve (AUC) values for single and multiple NTS applications were 14.0 and 15.8, respectively. The pharmacokinetics of nicotine and cotinine were linear between single and multiple NTS applications. The nicotine transdermal systems were generally well tolerated.

Nicotine delivery kinetics and abuse liability.

It is well established that nicotine meets all criteria of a highly addictive drug. However, as recognized by the U.S. surgeon general, the nicotine delivery system itself is an important determinant of the toxic and addictive effects engendered by nicotine use. Therefore, altering the form of nicotine dosing may allow for selective therapeutic action in efforts to develop safer and less addictive nicotine replacement therapies. While it is the case that initial tobacco use often escalates to compulsive use accompanied by tolerance and physical dependence, this is not usually observed with nicotine replacement therapies. These observations are consistent with laboratory data indicating that (a) nicotine polacrilex and transdermal systems deliver nicotine more slowly and at lower dose levels than tobacco-based forms, and (b) human data suggesting that the abuse liability of these systems is substantially lower than that of the tobacco-based nicotine delivery systems. Because the drug dosage form can be systematically manipulated and evaluated, further research in developing alternative nicotine delivery forms may hold substantial promise in the treatment of tobacco dependence. Psychological research methods can play an important part in their evaluation.

Transdermal Nicotine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an aid to smoking cessation.

Transdermal nicotine delivery systems are a cigarette smoking cessation aid designed to deliver nicotine into the systemic circulation via the skin. The partial replacement of plasma nicotine, which would have otherwise been obtained from cigarettes, reduces the severity of nicotine withdrawal symptoms, and so allows the smoker to abstain from smoking more easily. The systems are available in 16- and 24-hour application regimens, and are recommended for daily use for up to 20 weeks, including a series of 'weaning-off' courses. Clinical trials have shown that abstinence rates of 30 to 41% can be achieved during the first 6 weeks of application of transdermal nicotine systems, compared with 4 to 21% with placebo systems. The use of concomitant behavioural therapy may increase the success of treatment, with initial abstinence rates of up to 86% reported. However, long term abstinence rates (greater than 6 months) are considerably lower with or without behavioural therapy, often falling to less than half of the initial rates. Transdermal nicotine systems have been well tolerated in clinical trials, with local irritation at the site of application being the most common adverse event. Mild gastric, central nervous system (CNS) and sleep disturbances have also been reported. The ease of use and unobtrusive nature of the systems have resulted in a high degree of patient compliance. Thus, transdermal nicotine systems offer a convenient form of nicotine replacement therapy which are well tolerated and, due to their pharmacokinetic profile, probably have a low dependency potential. The short term abstinence rates achieved with this therapy are encouraging; however, the maintenance of abstinence in the long term is harder to achieve. Transdermal nicotine replacement therapy, therefore, represents an important advance in the difficult area of smoking cessation management.

Nicotine Transdermal System Receives Approval

Nicotine Transdermal System Receives Approval

A transdermal nicotine system: feasibility studies

The permeation of nicotine through human epidermis in vitro, membranes, adhesives, an adhesive-membrane laminate, and the laminate with epidermis was measured. Skin irritation in rabbits was shown to depend on the driving force of nicotine in the donor phase. A transdermal nicotine system is described that provides substantial control of nicotine entry through skin by a rate-controlling membrane.

Pharmacokinetic disposition of multiple-dose transdermal nicotine in healthy adult smokers.

The pharmacokinetics and cardiovascular effects of nicotine and its major metabolite, cotinine, were characterized during repeated once-daily application for 5 days of a 30-cm2 nicotine transdermal system, Nicotine TTS (Habitrol), to nine healthy, black, adult, male smokers. Subjects abstained from smoking throughout the study. Pharmacokinetic analysis indicated that nicotine was delivered from Nicotine TTS for the 24-hr application period averaging 0.76 mg/cm2/24 hr, and at a relatively constant rate compared to other modes of drug administration. The transdermal clearance of nicotine, 1351 ml/min, coincided with reported values following intravenous nicotine administration; however, the terminal-phase half-life, 5.0 hr, did not. An analysis of the components of variance contributing to the variability in nicotine delivery from repetitive application of Nicotine TTS indicated that the in vivo transdermal permeation of nicotine is rate limited by both the device and the intrinsic skin conductivity. Clinical cardiovascular side effects were negligible as an apparent result of subclinical vasopressive nicotine concentrations, although drug activity with regard to other effects was manifested.

Transdermal Nicotine for Smoking Cessation

Objective. —To evaluate the efficacy of a new transdermal nicotine system for smoking cessation. Design. —Two 6-week, randomized, double-blind, placebo-controlled, parallel group trials were conducted. Successful abstainers from both trials enrolled in a third trial for blinded downtitration from medications (6 weeks) and subsequent off-drug follow-up (12 weeks). Setting. —Nine outpatient clinics specializing in the treatment of smoking cessation. Patients. —Healthy volunteers who smoked one or more packs of cigarettes daily and wanted to participate in a smoking cessation program. Intervention. —Patients were randomly assigned to a transdermal nicotine system delivering nicotine at rates of 21,14, or 7 mg (in trial 1 only) over 24 hours or to placebo. Group counseling sessions were provided to all participants. Main Outcome Measure. —Rates of continuous smoking abstinence were determined during 6 weeks of full-dose treatment, a 6-week weaning period (through week 12), and a 3-month follow-up receiving no therapy (through week 24). Abstinence was defined by patient diary reports of no smoking during the designated periods, confirmed by expired-breath carbon monoxide levels of 8 ppm or lower. Results. —The centers enrolled 935 patients. Cessation rates during the last 4 weeks of the two 6-week trials (pooled data) were 61%, 48%, and 27% for 21-and 14-mg transdermal nicotine and placebo, respectively ( P ≤.001 for each active treatment vs placebo). Six-month abstinence rates for 21-mg transdermal nicotine and placebo were 26% and 12%, respectively ( P ≤.001). All transdermal nicotine doses significantly decreased the severity of nicotine withdrawal symptoms and significantly reduced cigarette use by patients who did not stop smoking. Compliance was excellent, and no serious systemic adverse effects were reported. Conclusions. —Transdermal nicotine systems show considerable promise as an aid to smoking cessation. ( JAMA . 1991;266:3133-3138)

Transdermal nicotine for smoking cessation. Six-month results from two multicenter controlled clinical trials. Transdermal Nicotine Study Group

To evaluate the efficacy of a new transdermal nicotine system for smoking cessation.Two 6-week, randomized, double-blind, placebo-controlled, parallel group trials were conducted. Successful abstainers from both trials enrolled in a third trial for blinded downtitration from medications (6 weeks) and subsequent off-drug follow-up (12 weeks).Nine outpatient clinics specializing in the treatment of smoking cessation.Healthy volunteers who smoked one or more packs of cigarettes daily and wanted to participate in a smoking cessation program.Patients were randomly assigned to a transdermal nicotine system delivering nicotine at rates of 21, 14, or 7 mg (in trial 1 only) over 24 hours or to placebo. Group counseling sessions were provided to all participants.Rates of continuous smoking abstinence were determined during 6 weeks of full-dose treatment, a 6-week weaning period (through week 12), and a 3-month follow-up receiving no therapy (through week 24). Abstinence was defined by patient diary reports of no smoking during the designated periods, confirmed by expired-breath carbon monoxide levels of 8 ppm or lower.The centers enrolled 935 patients. Cessation rates during the last 4 weeks of the two 6-week trials (pooled data) were 61%, 48%, and 27% for 21- and 14-mg transdermal nicotine and placebo, respectively (P less than or equal to .001 for each active treatment vs placebo). Six-month abstinence rates for 21-mg transdermal nicotine and placebo were 26% and 12%, respectively (P less than or equal to .001). All transdermal nicotine doses significantly decreased the severity of nicotine withdrawal symptoms and significantly reduced cigarette use by patients who did not stop smoking. Compliance was excellent, and no serious systemic adverse effects were reported.Transdermal nicotine systems show considerable promise as an aid to smoking cessation.

The use of transdermal nicotine in smoking cessation

The transdermal administration of nicotine by means of a transdermal nicotine system (TNS) affords a novel way of nicotine replacement to alleviate smoking cessation. The plasma levels of nicotine maintained with the TNS are in the range of the footpoint concentrations observed in smokers. The efficacy of the TNS was investigated in two placebo-controlled double-blind smoking cessation programs with minimal contact and minimal psychological support. A total of 311 smokers were treated for 3 months or 9 weeks. The abstinence rates at the end of the treatment and weaning periods were almost doubled in the TNS groups (36% and 39%) as compared to the placebo groups (23% and 20%) with a significant difference for both studies (p less than 0.05). These data suggest that the TNS can also improve the smoking cessation rates under the conditions of general medical advice, making it suitable for use outside of specialized smoking cessation centers.