Pharmacokinetics of a nicotine polacrilex lozenge.
To evaluate the pharmacokinetic characteristics of the 2-mg and 4-mg nicotine polacrilex lozenges, the following four separate studies were conducted in healthy adult smokers: (a) A single-dose, four-way crossover (replicate design) study to compare the 4-mg lozenge and the 4-mg nicotine polacrilex gum, (b) a single-dose, two-way crossover study to compare the 2-mg lozenge and the 2-mg gum, (c) a multiple-dose, four-way crossover study to compare the lozenges administered every 90 min and the gums administered every 60 min at 2- and 4-mg dose levels, and (d) a single-dose, three-way crossover study to compare the pharmacokinetic profiles of the 4-mg lozenge when administered in three different ways: (i) Used as directed, (ii) chewed and immediately swallowed, and (iii) chewed, retained in the mouth for 5 min, and then swallowed. The single-dose studies consistently demonstrated 8%-10% higher maximal plasma concentrations and 25%-27% higher AUC values (area under the concentration-time curve) from the lozenges compared with the gums at the 2- and 4-mg dose levels, probably owing to the residual nicotine retained in the gum. The multiple-dose study applying different dosing intervals (i.e., every 90 min for the lozenges and every 60 min for the gums) resulted in approximately 30% lower AUC(0-t) values for the lozenges compared with those for the gums. Administration of the lozenge contrary to the label-specified instructions for use did not lead to a faster or higher absorption of nicotine. These pharmacokinetic characteristics should allow the lozenge to become an effective and safe therapeutic alternative for smoking cessation.
GlaxoSmithKline Consumer Healthcare, Parsippany NJ 07054-3884, USA. jae.h.choi@gsk.com
Jae H
JH
Choi
Carolyn M
CM
Dresler
Michele R
MR
Norton
Kenneth R
KR
Strahs
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002638:Chewing Gum; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007475:Ion Exchange Resins; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011145:Polyvinyls / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016540:Smoking Cessation; D061485:Tobacco Use Cessation Devices; D014029:Tobacco Use Disorder / Q000188:drug therapy*
D000697:Central Nervous System Stimulants; D002638:Chewing Gum; D007475:Ion Exchange Resins; D011109:Polymethacrylic Acids; D011145:Polyvinyls; D009538:Nicotine