Search PubMed⌕ Search

Biomedical subjects

R D Hurt

Publications and source records attributed to R D Hurt.

At least 55 records · Page 3Linked to original sources
PubMed1998

A solid phase extraction method for determination of nicotine in serum and urine by isotope dilution gas chromatography/mass spectrometry with selected ion monitoring.

A rapid method for measuring nicotine concentration in serum and urine is described. Deuterated nicotine is used as an internal standard. Nicotine and deuterated nicotine are extracted using a copolymeric-bonded phase silica column. The extract is analysed by gas chromatography coupled with mass spectrometry (GC/MS) operating in selected ion monitoring mode. The method has a lower limit of detection of approximately 2 micrograms/L and is linear to at least 2000 micrograms/L. Within-run percentage coefficients of variation (% CV) are < 4 in both assays over a nicotine concentration range of 10-2000 micrograms/L. Between-run % CV in the serum assay are 5.4, 5.2, 4.8 and 5.9, respectively, at nicotine concentrations of 10, 15, 25, and 50 micrograms/L. Between-run % CV in the urine assay are 5.9, 4.5, 2.7 and 5.2, respectively, at nicotine concentrations of 100, 250, 500, and 2000 micrograms/L. The absolute recovery of nicotine is 61 +/- 6% (mean +/- SD) over the range of 10-250 micrograms/L. The assay has been used to measure serum nicotine concentrations and 24-h urinary excretion of nicotine to monitor the extent of replacement in subjects receiving transdermal nicotine therapy for smoking cessation.

Deuterium↗
PubMed1998

Trends in smoking-related diseases. Why smoking cessation is still the best medicine.

Although millions of Americans have kicked the habit, the effects of cigarette smoking likely will be around for a long time. What was once regarded as a glamorous habit is now recognized as a health threat and an economic burden. But what headway has been made in the reduction of related morbidity and mortality? The authors of this article review the current epidemiologic data on smoking-related diseases and make an indisputable case for smoking cessation.

Cardiovascular Diseases↗
PubMed1998

Drug therapy to aid in smoking cessation. Tips on maximizing patients' chances for success.

The arsenal of pharmacologic agents available for smoking cessation has expanded in the last few years, and it is likely to continue to do so. It is important that practicing physicians keep abreast of new methods as they become available and encourage patients who smoke to undertake cessation measures. Nicotine-replacement therapy is available in gum, patch, nasal spray, or inhaler form, and bupropion therapy aids in smoking cessation through dopaminergic activity. The foundation of effective intervention is likely to remain unchanged: an individualized plan addressing behavioral, addictive, pharmacologic, and relapse-prevention components. In addition to the necessary information about treatment choices, physicians should offer motivation, support, and follow-up to their patients who wish to quit smoking.

Administration, Cutaneous↗
PubMed1997

A comparison of sustained-release bupropion and placebo for smoking cessation.

BACKGROUND AND METHODS: Trials of antidepressant medications for smoking cessation have had mixed results. We conducted a double-blind, placebo-controlled trial of a sustained-release form of bupropion for smoking cessation. We excluded smokers with current depression, but not those with a history of major depression. The 615 subjects were randomly assigned to receive placebo or bupropion at a dose of 100, 150, or 300 mg per day for seven weeks. The target quitting date (or "target quit date") was one week after the beginning of treatment. Brief counseling was provided at base line, weekly during treatment, and at 8, 12, 26, and 52 weeks. Self-reported abstinence was confirmed by a carbon monoxide concentration in expired air of 10 ppm or less. RESULTS: At the end of seven weeks of treatment, the rates of smoking cessation as confirmed by carbon monoxide measurements were 19.0 percent in the placebo group, 28.8 percent in the 100-mg group, 38.6 percent in the 150-mg group, and 44.2 percent in the 300-mg group (P<0.001). At one year the respective rates were 12.4 percent, 19.6 percent, 22.9 percent, and 23.1 percent. The rates for the 150-mg group (P=0.02) and the 300-mg group (P=0.01) -- but not the 100-mg group (P=0.09) -- were significantly better than those for the placebo group. Among the subjects who were continuously abstinent through the end of treatment, the mean absolute weight gain was inversely associated with the dose (a gain of 2.9 kg in the placebo group, 2.3 kg in 100-mg and 150-mg groups, and 1.5 kg in the 300-mg group; P= 0.02). No effects of treatment were observed on depression scores as measured serially by the Beck Depression Inventory. Thirty-seven subjects stopped treatment prematurely because of adverse events; the frequency was similar among all groups. CONCLUSIONS: A sustained-release form of bupropion was effective for smoking cessation and was accompanied by reduced weight gain and minimal side effects. Many participants in all groups were smoking at one year.

Adult↗
PubMed1997

Transdermal nicotine for mildly to moderately active ulcerative colitis. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Ulcerative colitis is predominantly a disease of nonsmokers. Transdermal nicotine may help control clinical manifestations of this condition. OBJECTIVE: To determine the efficacy of transdermal nicotine for controlling clinical disease activity in active ulcerative colitis. DESIGN: Randomized, double-blind, placebo-controlled, single-center clinical trial. SETTING: Multispecialty group serving as an academic tertiary referral center. PATIENTS: 64 nonsmoking patients with mildly to moderately active ulcerative colitis despite the use of medication. INTERVENTION: Patients were stratified on the basis of smoking history, extent of disease, and concomitant medical therapy. After stratification, patients were randomly assigned to daily treatment with transdermal nicotine (n = 31) at the highest tolerated dose (11 mg for 1 week and then < or = 22 mg for 3 weeks) or placebo (n = 33). MEASUREMENTS: Clinical features were assessed at baseline and 4 weeks by endoscopy, physician assessment, and a patient diary of daily symptoms. Serum concentrations of nicotine were determined by using gas chromatography and mass spectrometry, and plasma concentrations of cotinine were measured by using high-performance liquid chromatography. RESULTS: At 4 weeks, 12 of 31 patients (39%) who received nicotine showed clinical improvement compared with 3 of 33 patients (9%) who received placebo (P = 0.007). Four patients receiving nicotine discontinued therapy because of side effects (contact dermatitis [n = 2], nausea [n = 1], and acute pancreatitis [n = 1]). At week 4, the nicotine group had a mean (+/-SD) trough serum nicotine concentration of 11.3 +/- 8.4 ng/mL and a mean trough plasma cotinine concentration of 192 +/- 95 ng/mL. CONCLUSIONS: Transdermal nicotine administered at the highest tolerated dosage (< or = 22 mg/d) for 4 weeks is efficacious for controlling clinical manifestations of mildly to moderately active ulcerative colitis.

Administration, Cutaneous↗
PubMed1997

Pharmacokinetics of nicotine tartrate after single-dose liquid enema, oral, and intravenous administration.

Ulcerative colitis is predominantly a disease of nonsmokers, and transdermal nicotine is therapeutic but often results in adverse reactions. Colonic administration of nicotine tartrate as a liquid enema could decrease systemic nicotine absorption and adverse reactions. The purpose of the current study was to determine the bioavailability and pharmacokinetic parameters of nicotine after administration by hydrophilic liquid enema (acidic and basic), hydrophobic liquid enema (acidic and basic), and by oral and intravenous routes. Thirty healthy volunteers received 45 micrograms nicotine base/kg (as nicotine tartrate) in one of five formulations (each n = 6): hydrophilic acidic liquid enema, hydrophilic basic liquid enema, hydrophobic acidic liquid enema, hydrophobic basic liquid enema, and oral solution. All participants also received 15 micrograms nicotine base/kg (as nicotine tartrate) intravenously during a separate study period. Serum concentrations of nicotine were determined by gas chromatography with mass spectrometry. The mean (+/-SD) bioavailabilities of nicotine after administration in the liquid enema formulations (hydrophilic acidic 17 +/- 18%, hydrophilic basic 16 +/- 16%, hydrophobic acidic 25 +/- 17%, hydrophobic basic 15 +/- 12%) were similar to the bioavailability of nicotine after administration by oral solution (20 +/- 25%). The bioavailabilities of nicotine for all five nonintravenous formulations were significantly less than for intravenous nicotine (100%). Serum concentrations of nicotine did not predict adverse reactions. Nicotine tartrate administered as either a liquid enema or as an oral solution had low bioavailability and was well tolerated. The therapeutic potential of nicotine tartrate liquid enemas, which can potentially limit toxicity by local (colonic) delivery of high doses of nicotine should be investigated in patients with left-sided ulcerative colitis.

Administration, Oral↗
PubMed1997

Cost-effectiveness of treating nicotine dependence: the Mayo Clinic experience.

OBJECTIVE: To estimate the cost-effectiveness of treating nicotine dependence, expressed as cost per net year of life gained by smoking cessation. DESIGN: A cost-effectiveness analysis was conducted of a cohort of consecutive adult patients treated for nicotine dependence from April 1988 through December 1992 at the Mayo Clinic Nicotine Dependence Center (NDC). MATERIAL AND METHODS: The study cohort consisted of 5,544 patients (50.8% female; mean age, 47.8 years) with a mean baseline smoking rate of 25.4 cigarettes per day. After an initial consultation, a nonphysician counselor developed an individual nicotine dependence treatment plan, which could include follow-up counseling, nicotine replacement therapy (patches or gum), group therapy, or an inpatient program. A relapse-prevention program included telephone calls and a series of letters to the patient. We computed the years of life gained for each person specific to age, gender, smoking rate at entry, and 6-month smoking status by using published mortality rates for current and former cigarette smokers. The 6-month smoking status was assumed to be applicable at 1 year. For subsequent determinations, we modeled by computer simulation the year-by-year (to age 100) smoking status by using published relapse and late cessation rates. Coupled with treatment costs, this information allowed the expression of cost per net year of life gained by stopping smoking. Net years of life gained, discounted 0, 3, and 5%, were computed with use of cessation and relapse rates expected for patients not seen in the NDC. Treatment costs were based on 1993 rates for the intervention services but did not include any tobacco product cost savings associated with smoking cessation. RESULTS: The 1-year smoking-cessation rate was 22.2%. With all NDC patients included, the estimated net years of life gained, with use of a 5% rate of discount for benefits, was 0.058, and the corresponding cost was $6,828 per net year of life gained. CONCLUSION: In comparison with the cost-effectiveness of other medical services, the cost of $6,828 per net year of life gained by treatment of nicotine dependence is relatively inexpensive. Such cost-outcome data are important as economic considerations are applied for optimal allocation of limited health-care resources. Nonphysician health-care professionals can assume a key role in the provision of cost-effective nicotine dependence intervention.

Adult↗
PubMed1997

Nicotine tartrate liquid enemas for mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy: a pilot study.

BACKGROUND: Ulcerative colitis is predominantly a disease of non-smokers, and transdermal nicotine is therapeutic but often results in side-effects. Administration of nicotine as a liquid rectal enema results in less systemic nicotine absorption. AIM: To determine the safety and clinical response of nicotine tartrate liquid enemas for active left-side ulcerative colitis in a pilot study. METHODS: Ten non-smoking patients with mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy were treated in an open protocol with nightly nicotine tartrate liquid enemas at a dose of 3 mg nicotine base for 1 week then 6 mg for 3 weeks. Clinical assessments were determined at baseline and 4 weeks by endoscopy, physician assessment and a patient diary of daily symptoms. Peak and trough serum nicotine and trough plasma cotinine were determined by gas chromatography/mass spectrometry and high performance liquid chromatography, respectively. RESULTS: After 4 weeks of treatment, 5/7 patients (71%) showed clinical and sigmoidoscopic improvement (per protocol analysis). The other three patients discontinued therapy within 7 days because of inability to retain the liquid enemas. No patients showed histologic improvement. Six of the patients who completed the 4-week study had peak and trough serum nicotine concentration determined, only 1 of 6 patients had a detectable peak nicotine concentration (value 2.3 ng/mL), and all six patients had undetectable trough nicotine concentrations. The mean trough plasma cotinine concentration was 13 +/- 10 ng/mL. Transient and mild adverse events occurred in 4/10 patients (nausea, lightheadedness, tremor, sleep disturbance). Given the low or undetectable serum nicotine concentrations, these adverse events are not likely to be related to the nicotine enemas. CONCLUSIONS: Nicotine tartrate liquid enemas administrated at a dose of 3 mg nicotine base/day for 1 week and then 6 mg/day for 3 weeks are safe and appear to result in clinical improvement in some patients with mildly to moderately active, left-sided ulcerative colitis unresponsive to first-line therapy. Placebo-controlled trials are warranted to confirm these preliminary findings.

Adult↗
PubMed1997

A dose-ranging pharmacokinetic study of nicotine tartrate following single-dose delayed-release oral and intravenous administration.

BACKGROUND: Ulcerative colitis is predominantly a disease of non-smokers, and transdermal nicotine is therapeutic but often results in side-effects. Administration of nicotine tartrate as a liquid enema decreases systemic nicotine absorption and may be effective for treatment of active distal ulcerative colitis. Ileocolonic delivery of nicotine tartrate via a delayed release oral capsule would be the preferred route to deliver nicotine to the colon. AIM: To determine the bioavailability and pharmacokinetic parameters of delayed-release oral nicotine tartrate capsules (Eudragit S100 coated) at doses of 3 mg and 6 mg nicotine. METHODS: Twenty healthy human subjects received delayed-release oral nicotine tartrate at one of two doses (each group n = 10): 3 mg and 6 mg nicotine. All subjects also received intravenous nicotine tartrate (at a dose of 15 micrograms nicotine base/kg) during a separate study period. Serum nicotine concentrations were determined by gas chromatography-mass spectrometry. In addition, concentrations of serum cotinine (major nicotine metabolite) were determined by high-performance liquid chromatography in all samples for two subjects (both given 6 mg nicotine). Adverse reactions were determined by questionnaire. RESULTS: The mean bioavailabilities of nicotine after ileocolonic nicotine tartrate administration via delayed-release oral capsules at doses 3 mg and 6 mg nicotine were 41% and 42%, respectively. The ratios (after adjusting for nicotine dose) of cotinine area under the curve (AUC) for delayed-release oral nicotine to cotinine AUC for intravenous nicotine were 1.5 and 1.6 for the two subjects undergoing cotinine pharmacokinetics, demonstrating significant first-pass metabolism. Serum nicotine concentrations did not predict adverse reactions. CONCLUSIONS: Nicotine tartrate delivered to the ileocolon as a delayed-release oral capsule at doses of 3 mg and 6 mg nicotine considerably reduced systemic nicotine bioavailability. This reduction in bioavailability appears to be a result of first-pass hepatic metabolism rather than poor mucosal absorption of nicotine. The therapeutic potential of an ileocolonic delivery formulation of nicotine tartrate, which can potentially limit toxicity by local delivery of high doses of nicotine, should be investigated in patients with ulcerative colitis.

Administration, Oral↗
PubMed1997

Predictors of smoking cessation among elderly smokers treated for nicotine dependence.

OBJECTIVE: To examine outcomes and predictors of smoking cessation among elderly patients treated for nicotine dependence. DESIGN: Retrospective analysis of patients aged 65-82 who received a nicotine dependence consultation at the Mayo Medical Center between 1 April 1988 and 30 May 1992. Patients were contacted by telephone by a trained interviewer six months after the consultation and were sent a follow-up survey in August 1993. SETTING: Mayo Medical Center, Rochester, Minnesota, United States. SUBJECTS: A total of 613 patients (310 men, 303 women) with a mean age of 69.0 (SD 3.5) years were seen during the study period. MAIN OUTCOME MEASURES: Point prevalence self-reported smoking status. Patients were considered abstinent if they self-reported not smoking (not even a puff) during the seven days before contact. RESULTS: At six-month follow up, 24.8% of the 613 patients reported abstinence from smoking. On multivariate analysis, smoking abstinence was more likely if patients were hospitalised at the time of the consultation, married to a non-smoking spouse, very motivated to stop smoking, and reported their longest time of previous abstinence to be less than a day or more than a month. The response rate to the mailed follow-up survey was 69.9% (429 of 613). The mean duration of follow up was 40.0 +/- 13.2 months following the consultation. Of the 429 patients, 103 (24.0%) reported abstinence from smoking and 326 (76.0%) were smoking at six-month follow up. Patients who reported abstinence at six months had a higher cessation rate at the last follow up (76.0%) compared with patients who were smoking at six-month follow up (33.0%, P < 0.001). For patients who were not smoking at six months, no factors were found to significantly predict abstinence at last follow up. For patients who were smoking at six months, factors associated with smoking cessation at last follow up were: more than a year as the longest time off cigarettes before the consultation; counsellor rating of less severe nicotine dependence; and older age at first regular smoking. CONCLUSIONS: Several predictors of smoking cessation were identified in this study which may be useful for tailoring smoking interventions for the elderly.

Aged↗
PubMed1996

Mortality following inpatient addictions treatment. Role of tobacco use in a community-based cohort.

OBJECTIVE: To determine the impact of tobacco- and alcohol-related deaths on overall mortality following inpatient treatment for alcoholism and other nonnicotine drugs of dependence. DESIGN: Population-based retrospective cohort study. SETTING: Olmsted County, Minnesota (the Rochester Epidemiology Project), and the Inpatient Addiction Program (IAP) at Mayo Clinic, Rochester. PATIENTS: All 845 Olmsted County residents admitted to an inpatient addiction program for treatment of alcoholism and other nonnicotine drugs of dependence during the period 1972 through 1983. METHODS: Patients were followed up through the medical record linkage system of the Rochester Epidemiology Project through December 1994 to obtain vital status, and death certificates were obtained for those who died. The underlying cause of death was classified as alcohol related, tobacco related, both, or neither based on the classification from the Centers for Disease Control and Prevention. The observed number of deaths by underlying cause were compared with the expected number using cause-specific 1987 death rates for the white population of the United States. All-cause mortality was also compared with that expected for persons in the West North Central Region of the United States of like age, sex, and year of birth. Univariate and multivariate assessments were made to identify predictors of all-cause mortality from baseline demographic information. RESULTS: At admission, the mean (SD) age of the 845 patients was 41.4 (14.5) years, and 35% were women. Altogether, 78% had alcohol as their only nonnicotine drug of dependence and 18% had alcohol and other nonnicotine drugs of dependence, while 4% were classified as having a nonalcohol, nonnicotine drug dependence alone. At admission, 75% were current and 8% former cigarette smokers, 3% were current cigar or pipe smokers, and 2% were current users of smokeless tobacco. Follow-up after the index IAP admission totaled 8913 person-years (mean [SD] of 10.5 [5.6] years per patient). Death certificates were obtained for 96% (214) of the 222 patients who died. Of these 214 deaths, 50.9% (109) had a tobacco-related and 34.1% (73) had an alcohol-related underlying cause (P<.001). The cumulative mortality significantly exceeded that expected (P<.001); at 20 years, the observed mortality was 48.1% vs an expected 18.5%. Multivariate predictors of mortality, even after adjusting for expected mortality, were older age at admission (P<.001) and male sex (P<.001). CONCLUSIONS: Patients previously treated for alcoholism and/or other nonnicotine drug dependence had an increased cumulative mortality that was due more to tobacco-related than to alcohol-related causes. Nicotine dependence treatment is imperative in such high-risk patients.

Adolescent↗
PubMed1996

Nicotine dependence versus smoking prevalence: comparisons among countries and categories of smokers.

OBJECTIVES: To collect available international data on nicotine dependence as defined by the Fagerström Test of Nicotine Dependence, and to compare levels of dependence among countries and categories of smokers. DATA SOURCES: Published and unpublished studies known to the authors and a search of EMBASE from 1985-1995. STUDY SELECTION: Studies included were those based on a nationally representative sample of a country's population, or a sample of smokers seeking cessation assistance. DATA SYNTHESIS: Smokers who seek help in stopping smoking are much more dependent than the average smoker. Men consistently score higher on dependence than women. Ex-smokers appear to have lower dependence than current smokers. A country with low smoking prevalence, the United States, seems to have smokers with higher dependence scores than countries where smoking is more prevalent (such as Austria and Poland). CONCLUSIONS: Successful tobacco control may result in a higher dependence among the remaining smokers (due to selective quitting by low-dependent smokers). The remaining highly dependent smokers may need more intensive treatment.

Culture↗
PubMed1996

Nicotine patch therapy in adolescent smokers.

OBJECTIVE: To evaluate the safety, tolerance, and efficacy of 24-hour nicotine patch therapy in adolescent smokers who were trying to stop smoking. DESIGN: Nonrandomized, open-label, 6-month clinical trial. SETTING: Five public high schools in the Rochester, MN, area. SUBJECTS: Twenty-two adolescent smokers, aged 13 through 17 years, with current smoking rate of 20 or more cigarettes per day (cpd). INTERVENTION: Daily nicotine patch therapy for 8 weeks (22 mg/d for 6 weeks followed by 11 mg/d for 2 weeks). Weekly individual behavioral counseling and group support continued for 8 weeks with follow up visits at 3 and 6 months and a mailed survey at 1 year. MAIN OUTCOME MEASURES: Self-reported smoking abstinence verified by expired air carbon monoxide of 8 ppm or less, nicotine withdrawal symptoms, adverse experiences, and blood cotinine levels. RESULTS: Subjects had a mean +/- SD smoking rate of 23.3 +/- 5.0 (range, 20 to 35) cpd at study entry and 2.6 +/- 1.6 years of smoking; the mean age was 15.9 +/- 1.2 (range 13 through 17) years, and 68% were girls. Of the 22 participants, 19 (86%) completed patch therapy, 3 (14%) had biochemically validated smoking cessation at week 8, and 1 continued to be smoke free at 3 and 6 months after patch initiation. There was a significant decrease from baseline in the mean nicotine withdrawal scores for days 4 and 7 of week 1 and the mean for weeks 2 through 8. Skin reactions were the most common adverse event. As the worst skin reactions, 55% had erythema only, 5% had erythema and edema, and 9% had erythema and vesicles, whereas 32% had no skin reactions. Other reported adverse events were headaches (41%), nausea and vomiting (41%), tiredness (41%), dizziness (27%), and arm pain (23%). None of these were considered serious, life threatening, or led to the discontinuation of patch therapy. In adults with comparable smoking rates, we found that the adolescents had lower blood cotinine levels. Those smoking 20 to 25 cpd had cotinine levels of 146 +/- 84 (adolescents) vs 260 +/- 98 (adults) ng/ml, and those smoking 26 to 35 cpd had levels of 169 +/- 73 vs 276 +/- 110 ng/ml, respectively. CONCLUSION: Nicotine patch therapy seems safe in adolescent smokers. Placebo-controlled trials are needed to establish the efficacy of nicotine patch therapy in adolescents.

Administration, Cutaneous↗
PubMed1995

Varying nicotine patch dose and type of smoking cessation counseling.

OBJECTIVE: To compare the efficacy and safety of 22-mg and 44-mg doses of transdermal nicotine therapy when it is paired with minimal, individual, or group counseling to improve smoking cessation rates. DESIGN: An 8-week clinical trial (4 weeks double-blind followed by 4 weeks open label) using random assignment of participants to both dose (22 or 44 mg) and counseling (minimal, individual, or group) conditions. PARTICIPANTS: Daily cigarette smokers (> or = 15 cigarettes per day for at least 1 year) who volunteered to participate in a study of smoking cessation treatment. A total of 504 participants were enrolled at two sites. INTERVENTION: Four weeks of 22- or 44-mg transdermal nicotine therapy followed by 4 weeks of dosage reduction (2 weeks of 22 mg followed by 2 weeks of 11 mg). Counseling consisted of a self-help pamphlet (minimal); a self-help pamphlet, a brief physician motivational message, and three brief (< 15 minutes) follow-up visits with a nurse (individual); or the pamphlet, the motivational message, and eight weekly 1-hour group smoking cessation counseling visits (group). All participants returned weekly to turn in questionnaires and for assessment of their smoking status. MAIN OUTCOME MEASURES: Abstinence from smoking was based on self-report, confirmed by an expired carbon monoxide concentration lower than 10 ppm. Withdrawal severity was assessed by means of an eight-item self-report questionnaire completed daily. RESULTS: Smoking cessation rates for the two nicotine patch doses and three levels of counseling did not differ significantly at either 8 weeks or 26 weeks following the quit date. Among those receiving minimal contact, the 44-mg dose produced greater abstinence at 4 weeks than did the 22-mg dose (68% vs 45%; P < .01). Participants receiving minimal-contact adjuvant treatment were less likely to be abstinent at the end of 4 weeks than those receiving individual or group counseling (56% vs 67%; P < .05). The 44-mg dose decreased desire to smoke more than the 22-mg dose, but this effect was not related to success in quitting smoking. Transdermal nicotine therapy at doses of 44 mg produced a significantly greater frequency of nausea (28%), vomiting (10%), and erythema with edema at the patch site (30%) than did a 22-mg dose (10%, 2%, and 13%, respectively; P < .01 for each adverse effect). Three serious adverse events occurred during use of the 44-mg patch dose. CONCLUSIONS: There does not appear to be any general, sustained benefit of initiating transdermal nicotine therapy with a 44-mg patch dose or of providing intense adjuvant smoking cessation treatment. The two doses and all adjuvant treatments produced equivalent effects at the 26-week follow-up, and the higher patch dose produced more adverse effects. Higher-dose (44-mg) nicotine replacement does not appear to be indicated for general clinical populations, although it may provide short-term benefit to some smokers attempting to quit with minimal adjuvant treatment.

Administration, Cutaneous↗
PubMed1995

High-dose nicotine patch therapy. Percentage of replacement and smoking cessation.

OBJECTIVE: To assess the level of nicotine replacement, evidence of nicotine toxicity, and withdrawal symptom relief with placebo and 11-, 22-, and 44-mg/d doses of transdermal nicotine. A secondary objective was to assess short- and long-term smoking cessation rates. DESIGN: Randomized, double-blind, placebo-controlled inpatient/outpatient trial. SUBJECTS: Seventy-one cigarette smokers stratified according to light (n = 23), moderate (n = 24), and heavy (n = 24) smoking rates. INTERVENTIONS: After baseline measures were obtained, subjects were randomly assigned to placebo or an 11-, 22-, or 44-mg/d dose of transdermal nicotine and admitted to a special hospital unit for intensive inpatient treatment of nicotine dependence. During the 6-day inpatient stay, daily nicotine and cotinine levels were determined from trough and peak blood samples. Outpatient patch therapy continued for 7 weeks following the hospital stay, and those initially assigned to placebo were randomly assigned to 11 or 22 mg/d. At week 4, the dosage of those initially assigned to 44 mg/d was reduced to 22 mg/d. MAIN OUTCOME MEASURES: Percentage of replacement of cotinine was calculated by dividing the steady-state levels attained during patch therapy by the corresponding baseline levels. Abstinence from smoking was verified by expired air carbon monoxide. Withdrawal symptoms and nicotine toxicity were assessed daily through questionnaires during the inpatient stay. Follow-up visits were at 3, 6, 9, and 12 months. RESULTS: There was a statistically significant relationship between baseline smoking rate and baseline trough and peak blood cotinine levels (rs = 0.39, rs = 0.45; P < .001 in both instances). A dose-response relationship was observed with higher patch doses, which produced a higher percentage of cotinine replacement and better withdrawal symptom relief. Only one subject (a light smoker assigned to the 44-mg dose) developed signs of nicotine toxicity. There was a positive association between the week 2 patch dose and the biochemically confirmed abstinence at the end of patch therapy (P = .007) but not for subsequent follow-up times. A higher percentage of cotinine replacement was associated with the higher 8-week smoking abstinence rate (P = .03), an association not found at long-term follow-up. CONCLUSION: A 44-mg/d dose of nicotine patch therapy appears to be safe for use in heavy smokers. Cigarette smoking rates can be used to estimate the initial nicotine patch dose. Monitoring blood cotinine levels at baseline and steady state can be used for assessing the adequacy of nicotine replacement. Withdrawal symptom relief can be improved with more complete nicotine replacement. Achieving a greater percentage of nicotine replacement may increase the efficacy of nicotine patch therapy.

Administration, Cutaneous↗