Evaluation of a Novel Nicotine Inhaler Device: Part 1—Arterial and Venous Pharmacokinetics

Introduction: In the United Kingdom, licensed nicotine-containing products can be recommended to reduce the harm associated with smoking. Many smokers find currently available nicotine replacement products unsatisfactory. The arterial and venous pharmacokinetics (PK) of nicotine delivered via a novel inhaler device were determined. Methods: Results are reported for Parts A (N = 18) and C (N = 18) of a 4-part (A-D) Phase I study. Participants (18-55 years, ≥10 cigarettes/day, smoking within 1 hr of w aking, expired carbon mon- oxide >10 ppm on screening) orally inhaled 2 single doses of nicotine (2 of 3 dose levels (0.22, 0.45, and 0.67 mg)) (Part A) and repeated hourly doses of 0.67 mg nicotine for 1 2 hr (P art C), via the novel device. Arterial and venous PK and tolerability were assessed. Results: In Part A, mean arterial plasma nicotine concentrations at 2 min af ter the start of inha- lation were 1.10, 2.06, and 2.59 ng/mL for the 0.22, 0.45, and 0.67 mg doses, respectively. Mean maximum arterial plasma nicotine concentrations (C max ) were 2.11, 3.73, and 4.38 ng/mL and mean times to C max were 10.2, 7.3, and 6.5 min af ter the start of inhalation for the 0.22, 0.45, and 0.67 mg doses, respecti vely. In Part C, the mean pre- and postdose venous plasma nicotine concentration increased steadily and fluctuated in the range 8-10 mg/mL af ter 9 hr . The novel device was well tolerated; most adverse events were mild. Conclusion: The novel inhaler device delivers nicotine rapidly into the systemic circulation and offers a viable alternative to cigarettes for those finding it difficult to quit the behavioral and senso- rial aspects of smoking.