Single-Dose Pharmacokinetics of Nicotine When Given With a Novel Mouth Spray for Nicotine Replacement Therapy

Abstract

As the efficacy of nicotine replacement therapy might be improved by faster systemic nicotine uptake, a new nicotine mouth spray has been developed. The current study was performed to evaluate the single-dose pharmacokinetics of nicotine at 3 doses of the mouth spray and to compare the speed of nicotine uptake from the spray versus nicotine lozenge and gum. In a randomized crossover study, 45 healthy adult smokers received single doses of nicotine mouth spray 1, 2, and 4 mg, nicotine lozenge 4 mg, and nicotine gum 4 mg on separate occasions. Blood samples were collected for 12 hr to determine pharmacokinetic variables. Mean plasma nicotine concentrations during the first 10 min, measured using area under the curve (AUC(10 min)), were 3 times as high with spray 4 mg as with lozenge or gum. The AUC(10 min) with 2 and 1 mg doses of spray, respectively, was twice and 1.5 times as high as the AUC(10 min) with lozenge or gum. The maximum baseline-corrected plasma nicotine concentration (cC(max)) with 4 mg spray exceeded that for lozenge and gum by 34% and 20%; the median time to reach C(max) was 10-12.5 min for the 3 doses of spray, 45 min for lozenge, and 30 min for gum. The mean baseline-corrected area under the plasma nicotine concentration-versus-time curve (cAUC(∞)) with 4 mg spray was 15% higher than that with gum but did not differ significantly from that with lozenge. Nicotine delivered via the mouth spray is absorbed considerably faster than nicotine given via gum or lozenge.