Objective: To evaluate the pharmacokinetics of a new 2-mg nicotine sublingu
al tablet under varying conditions of use.
Methods: The pharmacokinetics of the 2-mg nicotine sublingual tablet were i
nvestigated in four separate studies involving healthy adult volunteer smok
ers: (1) a multiple-dose comparison with 2-mg nicotine chewing gum (n=24; 1
3 males, 11 females), (2) a dose-proportionality study comparing single dos
es of 2, 4 and 6 mg (n=21, 10 males, 11 females), (3) an evaluation of the
effect of incorrect tablet use, i.e. chewing the tablet followed by either
immediate or delayed swallowing (n = 19, 10 males, 9 females), and (4) the
effect of oral and gastric pH on nicotine absorption from the tablet (n=20;
11 males, 9 females). Study parameters were maximal plasma concentration (
C-max), time to C-max (t(max)), and area under the plasma concentration-tim
e curve (AUC).
Results: The plasma nicotine profiles were similar following repeated admin
istration of the sublingual tablet and the 2-mg nicotine chewing gum (mean
C-max 13.2 versus 14.4 ng/ml, median t(max) 20 versus 20 min, mean AUC(11-1
2) 12.4 versus 13.5 ng/ml per hour) with no statistically significant diffe
rence between the two treatments. The pharmacokinetics of the 4- and 6-mg d
oses were non-linear compared to the 2-mg dose, probably as a result of mor
e of the dose being swallowed and undergoing first-pass metabolism in the l
iver. The mean C-max for the 2-, 4- and 6-mg dose was 3.8 +/- 1.0, 6.8 +/-
2.1, and 9.0 +/- 3.3 ng/ml, respectively, and in terms of dose proportional
ity the relative bioavailability of the 4- and 6-mg dose was 0.82 and 0.71,
respectively. Incorrect tablet use, i.e. chewing the tablet and immediate
swallowing decreased nicotine bioavailability both in terms of rate and ext
ent. Mean C-max was 12.1 ng/ml (correct use), 10.3 ng/ml (chewing and immed
iate swallowing), and 12.1 ng/ml (chewing and delayed swallowing). Correspo
nding mean values for AUC(9-10) were 11.6, 9.6 and 11.2 ng/ml per hour. The
re were no significant differences between 'alkaline mouth' versus control,
'acidic mouth' versus control or 'alkaline stomach' versus control, but the
rate of nicotine absorption was increased at alkaline compared to acidic o
ral pH (mean C-max 6.1 versus 4.9 ng/ml, P = 0.003; median t(max) 60 versus
90 min, P = 0.0002).
Conclusion: The pharmacokinetic profile of the nicotine 2-mg tablet was sim
ilar to that of the 2-mg nicotine chewing gum. Absorption of nicotine from
the tablet was nonlinear at higher doses (two or three tablets). Chewing th
e tablet and keeping the remains in the mouth or concurrent use of acidic b
everages or antacids are equivalent to recommended sublingual use during no
rmal oral pH conditions.