Hansson Anna, Rasmussen Thomas, Kraiczi Holger
Global Clinical Research, McNeil AB, Lund, Sweden.
Global Biometrics and Clinical Data Systems, McNeil AB, Helsingborg, Sweden.
Nicotine Tob Res. 2017 Apr 1;19(4):477-483. doi: 10.1093/ntr/ntw211.
Under-dosing is a recognized problem with current nicotine replacement therapy (NRT). Therefore, a new 6mg nicotine gum has been developed. To compare the nicotine uptake from the 6mg gum versus currently available NRT products, two pharmacokinetic studies were performed.
In one randomized crossover study, 44 healthy adult smokers received single doses of 6, 4, and 2mg nicotine gum, and 4mg nicotine lozenge on separate occasions. In a separate randomized crossover multiple-dose study over 11 hours, 50 healthy adult smokers received one 6mg gum every hour and 90 minutes, respectively, one 4mg gum every hour, and one 4mg lozenge every hour. In both studies, blood samples were collected over 12 hours to determine single-dose and multiple-dose pharmacokinetic variables.
In the single-dose study, the amount of nicotine released from the 2, 4, and 6mg gums (1.44, 3.36, and 4.94mg) as well as the resulting maximum concentration and area under the curve (5.9, 10.1, and 13.8ng/mL, and 17.1, 30.7, 46.2ng/mL × h, respectively) increased with dose. The maximum concentration and area under the curve of the 6mg gum were 44% and 30% greater, respectively, than those for 4mg lozenge. Upon hourly administration, the steady-state average plasma nicotine concentration with 6mg gum (37.4ng/mL) was significantly higher than those for 4mg lozenge (28.3ng/mL) and 4mg gum (27.1ng/mL).
Nicotine delivery via the 6mg gum results in higher plasma nicotine concentrations after a single dose and at steady state than with currently available oral NRT.
Under-dosing is a recognized problem with current NRT. Therefore, a new 6mg nicotine gum has been developed. Our studies show that upon single-dose and multiple-dose administration, the 6mg gum releases and delivers more nicotine to the systemic circulation than 2mg gum, 4mg gum, and 4mg lozenge. Thus, each 6mg nicotine gum provides a higher degree of nicotine substitution and/or lasts for a longer period of time than currently available nicotine gums and lozenges.
剂量不足是当前尼古丁替代疗法（NRT）中一个公认的问题。因此，已研发出一种新型6毫克尼古丁口香糖。为比较6毫克口香糖与现有NRT产品的尼古丁摄取量，进行了两项药代动力学研究。
在一项随机交叉研究中，44名健康成年吸烟者在不同时间分别接受6毫克、4毫克和2毫克尼古丁口香糖的单剂量，以及4毫克尼古丁含片。在另一项为期11小时的随机交叉多剂量研究中，50名健康成年吸烟者分别每小时、每90分钟服用一片6毫克口香糖，每小时服用一片4毫克口香糖，每小时服用一片4毫克含片。在两项研究中，均在12小时内采集血样以确定单剂量和多剂量药代动力学变量。
在单剂量研究中，2毫克、4毫克和6毫克口香糖释放的尼古丁量（分别为1.44毫克、3.36毫克和4.94毫克）以及由此产生的最大浓度和曲线下面积（分别为5.9纳克/毫升、10.1纳克/毫升和13.8纳克/毫升，以及17.1纳克/毫升·小时、30.7纳克/毫升·小时、46.2纳克/毫升·小时）均随剂量增加。6毫克口香糖的最大浓度和曲线下面积分别比4毫克含片高44%和30%。每小时给药时，6毫克口香糖的稳态平均血浆尼古丁浓度（37.4纳克/毫升）显著高于4毫克含片（28.3纳克/毫升）和4毫克口香糖（27.1纳克/毫升）。
与现有口服NRT相比，通过6毫克口香糖递送尼古丁在单剂量和稳态时可导致更高的血浆尼古丁浓度。
剂量不足是当前NRT中一个公认的问题。因此，已研发出一种新型6毫克尼古丁口香糖。我们的研究表明，在单剂量和多剂量给药时，6毫克口香糖比2毫克口香糖、4毫克口香糖和4毫克含片向体循环释放和递送更多的尼古丁。因此，每片6毫克尼古丁口香糖比现有尼古丁口香糖和含片提供更高程度的尼古丁替代和/或持续更长时间。
