INTRODUCTION: Many smokers find currently available nicotine replacement therapies unsatisfactory. The pharmacokinetics of nicotine delivered via a novel inhaler device, and its effect on craving satiation and smoking urges, were compared with the Nicorette® Inhalator (10 mg).METHODS: Results are reported for Parts B (N = 24) and D (N = 24) of a 4-part Phase I study. Participants (18-55 years, ? 10 cigarettes/day within 1 hr of waking, expired carbon monoxide >10 ppm on screening) received single doses of nicotine on consecutive days (0.45 and 0.67 mg [Part B] and 0.45 mg [Part D] via the novel device; 10 mg via Nicorette® [Parts B and D]). Venous pharmacokinetics, craving, and tolerability were assessed.RESULTS: In Part B, the novel device 0.45 and 0.67 mg produced significantly lower C max, AUClast, and AUCall than Nicorette® (all p ? .05), higher AUC0-10 and significantly shorter T max (18.7 and 19.2 min vs. 38.0 min, respectively, p ? .05). Craving score AUC was lower for the novel device 0.45 mg than for Nicorette® in Part B (1356.3 vs. 1566.3, p = .029) and approached statistical significance in Part D (1208.5 vs. 1402.3 [p = .059]). Mean craving scores were lower for the novel device 0.45 mg than Nicorette® at 7/8 postdose timepoints in Part B (p ? .05 at 180 and 240 min) and at all timepoints in Part D (p ? .05 at 2, 4, and 10 min).CONCLUSIONS: The novel device was at least as effective as the Nicorette® Inhalator (10mg) in relieving craving and smoking urges and was statistically superior at certain timepoints and in an overall craving AUC analysis, despite lower total nicotine exposure.
Administration, Inhalation Adolescent