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Transdermal Patch (transdermal + patch)

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Medical Sciences	100%

Selected Abstracts

Caregiver preference for rivastigmine patch relative to capsules for treatment of probable Alzheimer's disease

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2007
Bengt Winblad
Abstract Background Family caregivers comprise a critical component in the care of Alzheimer's disease (AD) patients. Among their many tasks, caregivers are responsible for administering and managing medications. Effective interventions incorporate the needs of both the AD patient and the caregiver, and understanding treatment preferences may maximize intervention effectiveness. Transdermal patches may offer advantages over conventional oral formulations. Methods A 24-week randomized controlled trial compared the rivastigmine patch to the rivastigmine capsule and placebo in patients with probable AD. At baseline and Weeks 8 and 24, the AD Caregiver Preference Questionnaire (ADCPQ) was used to evaluate caregiver expectations, preferences and satisfaction with treatment. Double-dummy treatment blinding ensured that caregiver preference for the patch or capsule was not confounded by perceptions of efficacy or tolerability. Reasons for preference were also elicited. The analytic sample included caregivers who completed the ADCPQ at Weeks 8 and/or 24. Results One thousand and fifty-nine caregivers completed the ADCPQ. More than 70% of caregivers preferred the rivastigmine patch to the capsule. The patch was significantly preferred to the capsule with respect to ease of following the schedule and ease of use. Caregivers indicated greater satisfaction overall, greater satisfaction with administration, and less interference with daily life with the patch versus the capsule (all p,,,0.01). Conclusion Caregivers of AD patients preferred the patch to the capsule for drug delivery. Preference for the rivastigmine patch could potentially lead to improved compliance and improved clinical benefits. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Evidence for lymphatic transport of insulin by topically applied biphasic vesicles

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2003
Martin J. King
ABSTRACT The cutaneous delivery pathway through the lymphatics of a novel transdermal lipid-based delivery system (biphasic vesicles), which was previously shown to deliver sustained physiological levels of basal insulin in a pain-free manner across the skin, was evaluated in a diabetic rat model. Transdermal patches (one per rat) containing insulin in biphasic vesicles (1,10 mg recombinant human insulin dose) were applied to the shaved abdominal skin of streptozotocin-induced diabetic rats for 73 h. Blood glucose was monitored approximately every 2,10 h using a Lifescan glucose meter. Inguinal lymph node insulin levels were analysed by ELISA. Insulin in the lymph nodes increased in a dose- and time-dependent manner. Maximal transdermal insulin concentrations in the lymph nodes were observed with both 140 IU (5 mg: 43.0 + 18.0 ,IU mg,1 (mean + s.e.m., n = 4)) and 280 IU (10 mg: 48.0 + 19.6 ,IU mg,1 (mean + s.e.m., n = 4)) doses of recombinant insulin at t = 73 h. The level of insulin in the lymph nodes after subcutaneous injection of 1 mg insulin at the peak blood glucose response was 35.8 ,IU mg,1 (n = 2), before falling to 0.35 ,IU mg,1 by t = 48 h (n = 2). The lymphatics is involved in the transdermal insulin delivery by biphasic vesicles. This is the first report on the lymphatic transport of a protein after non-invasive topical application on the skin. [source]

The effects of transdermal nicotine on inspection time

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 3 2002
J. C. Thompson
Abstract Rationale The acute administration of nicotine via a cigarette has been demonstrated to enhance inspection time (IT), a measure of rapid visual information processing, while the nicotinic antagonist mecamylamine impairs IT. However, as transdermal nicotine patches provide a slow delivery of nicotine, it is unclear if they produce similar effects to nicotine administered by more rapid methods. Objectives To examine the effects of transdermal nicotine on inspection time. Methods Ten moderate smokers were administered nicotine (21,mg/day) or placebo via a transdermal patch in a randomized, double-blind, repeated measures design. Subjects were administered the IT task at baseline, then 1, 3, and 6,h subsequent to patch application. Results The change in IT from baseline was significantly different in the nicotine condition, relative to placebo, at 3,h but not 1 or 6,h. Conclusions The findings suggest that nicotine administered via transdermal patches improves IT, but this improvement may be subject to tolerance. Data from previous studies on tolerance to the cognitive effects of nicotine have been inconclusive. However, the slow delivery of nicotine from patches may be more likely to produce such effects. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Pharmacokinetics of a novel transdermal rivastigmine patch for the treatment of Alzheimer's disease: a review

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2009
A. Kurz
Summary Background:, Cholinesterase inhibitors have all been available in oral formulations, but a rivastigmine transdermal patch has now been developed and is approved in many countries worldwide for the treatment of mild-to-moderate Alzheimer's disease (AD) (including the USA, Latin America, Europe and Asia). Objectives:, To review the available pharmacokinetic data that supported the rationale behind the development of the rivastigmine transdermal patch and its clinical effects in dementia therapy. This article will also discuss how the patch may alter the treatment paradigm for patients with AD. Results:, The 9.5 mg/24 h rivastigmine patch was shown to provide comparable exposure to the highest recommended doses of capsules (12 mg/day) with significantly lower maximum plasma concentration (Cmax 8.7 vs. 21.6 ng/ml) and slower absorption rate (tmax 8.1 vs. 1.4 h). In a clinical trial of 1195 AD patients, this translated into similar efficacy with three times fewer reports of nausea and vomiting (7.2% vs. 23.1%, and 6.2% vs. 17.0% respectively). Consequently, more patients in the 9.5 mg/24 h patch group achieved their target therapeutic dose at the end of the study, compared with those in the 12 mg/day capsule group (95.9% vs. 64.4%). Conclusion:, The rivastigmine patch provides continuous drug delivery over 24 h and similar efficacy to the highest recommended dose of oral rivastigmine with improved tolerability. This may allow patients to achieve optimal therapeutic doses and to benefit from a longer duration of treatment. [source]

Rotigotine improves restless legs syndrome: A 6-month randomized, double-blind, placebo-controlled trial in the United States,,§

MOVEMENT DISORDERS, Issue 11 2010
Wayne A. Hening MD
Abstract This randomized, double-blinded, placebo-controlled trial (NCT00135993) assessed efficacy and safety of the dopamine agonist rotigotine in the treatment of idiopathic restless legs syndrome (RLS) over a 6-month maintenance period. A total of 505 eligible participants with moderate to severe RLS (IRLS sum score , 15) were randomly assigned to five groups to receive either placebo or rotigotine (0.5, 1, 2, or 3 mg/24 hr) delivered by once-daily transdermal patch (fixed-dose regimen). The two co-primary efficacy parameters decreased from baseline to end of maintenance in IRLS sum score and in clinical global impressions (CGI-1) score. On both primary measures, 2 and 3 mg/24 hr rotigotine was superior to placebo (P < 0.001). Adjusted treatment differences to placebo for the IRLS sum score were ,4.5 (95% CI: ,6.9, ,2.2) for 2 mg/24 hr rotigotine, ,5.2 (95% CI: ,7.5, ,2.9) for 3 mg/24 hr rotigotine, and for CGI item 1 ,0.65 (95% CI: ,1.0, ,0.3) and ,0.9 (95% CI: ,1.3, ,0.5) for the 2 and 3 mg/24 hr doses, respectively. Skin reactions (27%) and known dopaminergic side effects such as nausea (18.1%) and headache (11.6%) were mostly mild or moderate in rotigotine subjects. Rotigotine transdermal patches releasing 2 to 3 mg/24 hr significantly reduced the severity of RLS symptoms. Treatment efficacy was maintained throughout the 6-month double-blind period. © 2010 Movement Disorder Society [source]

Latest news and product developments

PRESCRIBER, Issue 22 2007
Article first published online: 28 DEC 200
Glitazones: benefits outweigh the risks Following a review of the safety of rosiglitazone and pioglitazone, the European Medicines Agency (EMEA) has concluded that their benefits outweigh their risks in the approved indications. The review was prompted by reports of an increased risk of fractures in women and, in patients taking rosiglitazone, ischaemic heart disease. The EMEA concluded that prescribing information for rosiglitazone should now include a warning that, in patients with ischaemic heart disease, it should only be used after careful evaluation of each patient's individual risk, and the combination of rosiglitazone and insulin should only be used in exceptional cases and under close supervision. No change was considered necessary to the prescribing information for pioglitazone. Modern dressings no better? A systematic review has found only weak evidence that modern dressings are better than saline gauze or paraffin gauze for healing acute and chronic wounds (Arch Dermatol 2007;143: 1297-304). The analysis, which included 99 studies, found that only hydrocolloids were demonstrably better than older dressings for healing chronic wounds, and alginates were superior to other modern dressings for debriding necrotic wounds. There was no evidence that modern dressings offered superior overall performance to the older alternatives. Hospital inflation twice primary care level The cost of drugs prescribed in secondary care but dispensed in the community increased by 6.4 per cent in 2006 - twice the rate of inflation in primary care - according to the latest statistics on hospital prescribing in England. The increase follows a reduction in costs in 2005 after the introduction of the new PPRS scheme. Data from The Information Centre (www.ic.nhs.uk) show that hospital medicines make up about 24 per cent of the NHS drugs budget. Secondary care has a consistently better record than primary care in prescribing lower-cost alternatives within therapeutic categories, eg simvastatin and pravastatin among the statins, omeprazole and lansoprazole among PPIs, and ACE inhibitors among drugs acting on the renin angiotensin system. The most expensive drug prescribed by hospital specialists and dispensed in the community is interferon beta. MHRA limits the use of fibrates The Medicines and Healthcare products Regulatory Agency (MHRA) has advised that fibrates should now be reserved for the treatment of isolated severe hypertriglyceridaemia. They should be considered for hypercholesterolaemia only when a statin or other treatment is contraindicated or not tolerated. In the latest Drug Safety Update, the MHRA says there is insufficient evidence of long-term benefits from fibrates, and first-line use is no longer justified because the evidence for the benefits of statins is robust. The MHRA also warns that some breastfeeding infants have increased susceptibility to the adverse effects of codeine taken by their mother, and that St John's wort may affect the hepatic metabolism of any anticonvulsant. Annual zoledronic acid infusion cuts mortality after hip fracture Once-yearly infusion of zoledronic acid (Aclasta) after hip fracture reduces deaths over a two-year period by 28 per cent compared with placebo, US investigators say (N Engl J Med 2007;357:1799-809). The HORIZON Recurrent Fracture Trial randomised 2127 men and women (mean age 75) within 90 days of surgery for hip fracture to zoledronic acid 5mg yearly or placebo. Mortality over 1.9 years of follow-up was 9.6 per cent with zoledronic acid and 13.3 per cent with placebo. Zoledronic acid also significantly reduced the rate of any new clinical fractures (by 35 per cent) and new clinical vertebral fractures(by 45 per cent),but the lower rate of hip fracture (2.0 vs 3.5 per cent with placebo) was not statistically significant. Rivastigmine patch for mild to moderate AD Rivastigmine (Exelon) is now available as a transdermal patch for the treatment of mild to moderate Alzheimer's disease. Applied once daily, the patch delivers 9.5mg per 24 hours and, says manufacturer Novartis, is associated with a lower incidence of nausea and vomiting than a comparable oral dose. The patch is available in two strengths: 4.6mg per 24hr is equivalent to oral doses of 3 or 6mg per day, and the 9.5mg per 24hr patch is equivalent to 9 or 12mg per day orally. The recommended dose of the patch is 9.5mg per day; both strengths cost £83.84 for 30 patches. Women more aspirin resistant than men? The cardioprotective effect of low-dose aspirin may be lower in women than men, say Canadian investigators (BMC Medicine 2007;5:29 doi: 10.1186/1741-70155-29). Their meta-analysis of 23 randomised trials involving a total of 113 494 participants found that aspirin significantly reduced the risk of nonfatal but not fatal myocardial infarction (MI). About one-quarter of the variation in its effects on nonfatal MI was accounted for by the sex mix of the trial population. Separating the results by sex showed the reduction in risk with aspirin use was statistically significant in men (relative risk, RR, 0.62) but not in women (RR 0.87). Look after physical health of mentally ill GPs and other primary care workers should take more responsibility for the physical health of their mentally ill patients, say advocacy groups. Mind and Body: Preventing and Improving Physical Health Problems in Patients With Schizophrenia points out that the mental health needs of patients with schizophrenia are met in secondary care, but their physical health needs should be met in primary care. In particular, the metabolic effects of antipsychotics may lead to obesity, diabetes and cardiovascular disease, and weight gain in particular is a frequent reason for nonadherence to treatment. The Mind and Body Manifesto was developed by SANE, The Mental Health Nurses Association, The National Obesity Forum and The Disability Rights Commission and sponsored by Bristol-Myers Squibb Pharmaceuticals Limited and Otsuka Pharmaceuticals (UK) Ltd. Copies are available from elizabeth.green@ ogilvyhealthworld.com. Health eCard costs Some costs quoted in our article on the Health eCard (The Health eCard: the way ahead for medical records?,5 October issue, pages 28-9) have been revised: the card and initial download will cost patients £39.50, and GPs will be entitled to charge patients £10 per annum for subsequent downloads. NICE appraisals of cytokine inhibitors in RA NICE has endorsed the use of the anti-TNF agents adalimumab (Humira), etanercept (Enbrel) and infliximab (Remicade), normally in conjunction with methotrexate, for the treatment of active RA when methotrexate and another DMARD have failed (also see New from NICE below). NICE has provisionally concluded, subject to consultation, that abatacept (Orencia) should not be recommended for the treatment of RA. Boots and BMJ launch health advice site www.askbootshealth.com is a new website providing information about health and medicines for the public produced by Boots using information provided by the BMJ Publishing Group. The website covers many of the topics already available from NHSDirect, with perhaps more information about available treatments. Diabetes care shows small improvement The third National Diabetes Audit in England and Wales has found that more people with diabetes were achieving the targets set by NICE for cholesterol levels, glycaemic control and blood pressure in 2005/06 - but younger patients were doing less well. Overall, the HbA1C target of ,7.5 per cent was achieved in 60 per cent of people with diabetes compared with 58 per cent in 2004/05. However, HbA1C was >9.5 per cent in 30 per cent of children and young people, of whom 9 per cent experienced at least one episode of ketoacidosis. More topics for NICE New topics referred to NICE include clinical guidelines on ovarian cancer, coeliac disease and stable angina, public health guidance on preventing cardiovascular disease, and technology appraisals on insulin detemir (Levemir) for type 1 diabetes, several treatments for cancer and hepatic and haematological disorders, and biological therapies for juvenile arthritis. New from NICE NICE appraisal on anti-TNFs for RA Since NICE published its first appraisal of agents acting against tumour necrosis factor-alpha (anti-TNFs) for the treatment of RA in 2002, the product licences for etanercept (Enbrel) and infliximab (Remicade) have changed and a new agent, adalimumab (Humira), has been introduced. The anti-TNFs act in different ways. Infliximab is a chimeric monoclonal antibody that binds to TNF-alpha, neutralising its activity. Etanercept, a recombinant human TNF-alpha receptor fusion protein, and adalimumab, a human-sequence antibody, both bind to TNF-alpha and block its interaction with cell surface receptors. Adalimumab also modulates some biological responses induced or regulated by TNF-alpha. These agents are recommended for adults with severe active RA (defined as a disease activity score - DAS28 - greater than 5.1) who have already tried two disease-modifying drugs, including methotrexate (if not contraindicated). Prior treatment should have been of at least six months' duration, including two months at the standard dose (unless limited by toxicity). Anti-TNFs should normally be prescribed with methotrexate; when this is not appropriate, etanercept and adalimumab may be prescribed as monotherapy. Treatment with an anti-TNF should be continued beyond six months only if there is an adequate response (defined as an improvement in DAS28 of at least 1.2). Data from the British Rheumatology Society Biologics register show that, after six months, 67 per cent of patients met NICE criteria for an adequate response; this declined to 55 per cent at 18 months. The basic annual cost of treatment is £9295 for adalimumab 40mg on alternate weeks or etanercept 25mg twice weekly; infliximab costs £3777 for a loading dose, then £7553-£8812 depending on dose. Assuming no progression of disability, the incremental costs per QALY (compared with sequential DMARDs) were £30 200 for adalimumab, £24 600 for etanercept and £39 400 for infliximab. There are no direct comparative trials of the anti-TNFs, and their clinical trial findings are not directly comparable. Unless other factors determine treatment choice, NICE therefore recommends the least expensive. If the first anti-TNF is withdrawn within six months due to an adverse event, a second may be tried. [source]

Rotigotine: first dopamine agonist transdermal patch

PRESCRIBER, Issue 4 2007
Vinod Metta MB BS
Rotigotine (Neupro) is the first dopamine agonist skin patch to become available. Our New products review considers the clinical-trial evidence for its efficacy and tolerability in the treatment of early and advanced Parkinson's disease. Copyright © 2007 Wiley Interface Ltd [source]

Evaluation of a diclofenac transdermal patch for the attenuation of venous cannulation pain: a prospective, randomised, double-blind, placebo-controlled study

ANAESTHESIA, Issue 4 2006
A. Agarwal
Summary Venous cannulation, although a minor procedure, is often painful. The present study was planned to evaluate the efficacy of a diclofenac transdermal patch placed over the venepuncture site in decreasing the pain of cannulation. Seventy-two adults undergoing elective surgery were included in this randomised, prospective, double-blind, placebo-controlled study. Patients were divided into three equal groups. The Control group had a placebo adhesive patch placed on the both the dorsum of hand and the buttock; the Diclofenac-Buttock group had a placebo patch placed on the dorsum of the hand and a diclofenac transdermal patch on the buttock; the Diclofenac-Hand group had a diclofenac transdermal patch placed on the dorsum of hand and a placebo patch on the buttock. The patches were applied 1 h before cannulation. An 18G cannula was used for all venous cannulations. Pain during cannulation was assessed on a non-graduated 10-cm visual analogue scale. Median [interquartile range] pain scores were 3.0 [2.0,4.0] in the Diclofenac-Hand group, 5.0 [4.3,7.8] in the Diclofenac-Buttock group and 6.5 [4.5,7.0] in the Control group, p < 0.05. The numbers needed to treat were six and two in the Diclofenac-Buttock and Diclofenac-Hand groups, respectively. The application of a diclofenac transdermal patch at the cannulation site appears to be effective in decreasing cannulation pain. [source]

Ten-year survival outcome of the nicotine transdermal patch with cognitive behavioural therapy

AUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 3 2007
Robyn L. Richmond
Abstract Objective: To follow-up abstainers from the end of their initial treatment over seven points to 10 years. Methods: In the original study there were 305 smokers who were recruited in a double-blind randomised controlled trial. Those subjects who had remained continuously abstinent to seven years (n=20) were followed up to ascertain continuous smoking prevalence to 10 years. Main outcome measure was continuous abstinence. Results: At 10 years, the active nicotine patch group showed significantly higher continuous abstinence rates that were double those of the placebo group (7.9% vs. 2.6%, respectively). The high rate of relapse declined after six months. Conclusions: The nicotine patch leads to superior continuous abstinence over 10 years when compared with placebo. Public health implications: This is the longest follow-up study of continuous smoking abstinence after cognitive behaviour treatment combined with the nicotine patch. [source]

The effects of transdermal nicotine on inspection time

Alternate delivery route for amifostine as a radio-/chemo-protecting agent

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2008
Natalie P. Praetorius
Amifostine (ethiofos, WR-2721) is an organic thiophosphate prodrug that serves as an antineoplastic adjunct and cytoprotective agent useful in cancer chemotherapy and radiotherapy. The selective protection of certain tissues of the body is believed to be due to higher alkaline phosphatase activity, higher pH and vascular permeation of normal tissues. Amifostine is conventionally administered intravenously before chemotherapy or radiotherapy. It is approved by the Food and Drug Administration (FDA) to reduce cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer. It was originally indicated to reduce the cumulative renal toxicity from cisplatin in non-small cell lung cancer although this indication was withdrawn in 2005. Amifostine is also FDA approved for patients with head and neck cancer to reduce the incidence of moderate to severe xerostomia in patients who are undergoing postoperative radiation treatment where the radiation port includes a substantial portion of the parotid glands. The potential of amifostine as a cytoprotective agent is unlikely to be fully realized if the method of administration is restricted to intravenous administration. Attempts have been made to develop non-invasive methods of delivery such as transdermal patches, pulmonary inhalers, and oral sustained-release microspheres. It is the goal of this article to explore non-intravenous routes of administration associated with better efficacy of the drug. This review will primarily focus on the variety of more recently studied (2002 and later) alternative modes for amifostine administration, including subcutaneous, intrarectal and oral routes. [source]

Rotigotine improves restless legs syndrome: A 6-month randomized, double-blind, placebo-controlled trial in the United States,,§

Improved patient acceptability with a transdermal drug-in-adhesive oestradiol patch

AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 3 2000
Yvonne Lake
SUMMARY The aim of this trial was to assess the relative patient acceptability of two transdermal oestradiol patches used in treatment of oestrogen deficiency in postmenopausal women. Thirty-five hysterectomised postmenopausal women with no previous experience of transdermal oestradiol delivery systems received treatment with either once-weekly drug-in-adhesive (DIA) patches or twice-weekly reservoir patches for 4 weeks, and were then switched to the alternative treatment for a further 4 weeks. At the end of the study, the patients completed a questionnaire to assess their relative preference for a number of characteristics of the 2 transdermal systems and, where possible, their preference for transdermal compared with oral hormone replacement therapy. Thirty-one patients completed the study; four withdrew during treatment with the reservoir patch. The DIA patch was preferred for being ,easiest to remember to apply' by 80% of patients (p < 0.01), ,easiest to open' and ,easiest to apply' by 68% (p = 0.025), and as having ,best cosmetic appearance' by 65% (p = 0.05) and ,best overall skin adhesion' by 61% (p < 0.01). While 10% of patients rated the reservoir patch as ,least irritating to the skin' (p = 0.03), only one patient found this patch ,most comfortable to wear' (p < 0.01). The DIA patch was selected by 87% of patients as their preferred treatment overall (p = 0.001). Ninety-one per cent of 22 responding patients were at least as confident of treatment with transdermal patches as with oral hormone replacement therapy (p = 0.006) and 74% of 27 responders preferred transdermal to oral treatment (p = 0.004). The DIA patch appears to be more acceptable to patients than the reservoir patch as a transdermal oestradiol delivery system for the treatment of postmenopausal oestrogen deficiency. Characteristics of the DIA patch which may account for improved patient acceptance include ease of remembering once-weekly patch application, improved cosmetic appearance and comfort, and better adhesion. [source]

Effects of nicotine on cytochrome P450 2A6 and 2E1 activities

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2010
Janne Hukkanen
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Smoking slows the metabolism of nicotine and accelerates the metabolism of chlorzoxazone. , Nicotine is a useful probe for phenotyping cytochrome P450 2A6 activity and chlorzoxazone is a frequently used probe for CYP2E1 activity. , The tobacco smoke constituents responsible for the reduced CYP2A6 and increased CYP2E1 activities are unknown. WHAT THIS PAPER ADDS , This study demonstrates that CYP2A6 and CYP2E1 activities are not affected by nicotine dosing. , High-dose nicotine treatment has a low potential of interaction with CYP2A6 and CYP2E1 substrates. , The mechanisms of tobacco smoke-elicited changes in CYP2A6 and CYP2E1 activities are yet to be determined. AIMS Smoking slows the metabolism of nicotine and accelerates the metabolism of chlorzoxazone, which are probe reactions for cytochrome P450 2A6 (CYP2A6) and CYP2E1 activities, respectively. We aimed to determine the role of nicotine in these metabolic effects of cigarette smoking. METHODS The study had a single-blind, randomized, crossover two-arm design. Twelve healthy smokers were given two transdermal patches with 42-mg nicotine a day or placebo patches, each for 10 days. The subjects abstained from smoking during the study arms. Oral chlorzoxazone was given on day 7 and deuterium-labelled nicotine-d2 and cotinine-d4 infusion on day 8. RESULTS There was no significant influence of transdermal nicotine administration on pharmacokinetic parameters of nicotine-d2 or on the formation of cotinine-d2. Nicotine decreased the volume of distribution (62.6 vs. 67.7 l, 95% confidence interval of the difference ,9.7, ,0.6, P= 0.047) of infused cotinine-d4. There were no significant differences in disposition kinetics of chlorzoxazone between the treatments. CONCLUSIONS CYP2A6 and CYP2E1 activities are not affected by nicotine. The tobacco smoke constituents responsible for the reduced CYP2A6 and increased CYP2E1 activities remain unknown. [source]