Dale L C, Hurt R D, Offord K P, Lawson G M, Croghan I T, Schroeder D R
Division of Community Internal Medicine, Mayo Clinic, Mayo Foundation, Rochester, MN 55905, USA.
JAMA. 1995 Nov 1;274(17):1353-8.
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.
Randomized, double-blind, placebo-controlled inpatient/outpatient trial.
Seventy-one cigarette smokers stratified according to light (n = 23), moderate (n = 24), and heavy (n = 24) smoking rates.
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.
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.
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.
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.
评估尼古丁替代水平、尼古丁毒性证据以及使用安慰剂和每日11毫克、22毫克和44毫克剂量的经皮尼古丁缓解戒断症状的情况。次要目的是评估短期和长期戒烟率。
随机、双盲、安慰剂对照的住院/门诊试验。
71名吸烟者，根据轻度（n = 23）、中度（n = 24）和重度（n = 24）吸烟率进行分层。
在获得基线测量值后，受试者被随机分配到安慰剂组或每日11毫克、22毫克或44毫克剂量的经皮尼古丁组，并入住一家专门的医院科室，接受尼古丁依赖的强化住院治疗。在为期6天的住院期间，通过血样谷值和峰值测定每日尼古丁和可替宁水平。住院后门诊贴片治疗持续7周，最初分配到安慰剂组的患者被随机分配到每日11毫克或22毫克组。在第4周，最初分配到每日44毫克组的患者剂量减至每日22毫克。
可替宁替代百分比通过将贴片治疗期间达到的稳态水平除以相应的基线水平来计算。通过呼出气体一氧化碳验证戒烟情况。在住院期间通过问卷每日评估戒断症状和尼古丁毒性。随访时间为3、6、9和12个月。
基线吸烟率与基线血样谷值和峰值可替宁水平之间存在统计学显著关系（rs = 0.39，rs = 0.45；两者P均 <.001）。观察到贴片剂量越高，可替宁替代百分比越高，戒断症状缓解越好，存在剂量反应关系。只有一名受试者（一名分配到44毫克剂量的轻度吸烟者）出现尼古丁毒性迹象。第2周贴片剂量与贴片治疗结束时经生化确认的戒烟之间存在正相关（P = 0.007），但在后续随访时不存在。可替宁替代百分比越高，8周戒烟率越高（P = 0.03），长期随访时未发现这种关联。
每日44毫克剂量的尼古丁贴片疗法对重度吸烟者似乎是安全的。吸烟率可用于估计初始尼古丁贴片剂量。监测基线和稳态血样可替宁水平可用于评估尼古丁替代的充分性。更完全的尼古丁替代可改善戒断症状缓解情况。实现更高百分比的尼古丁替代可能会提高尼古丁贴片疗法的疗效。
