Evaluation of a novel nicotine inhaler device: part 1--arterial and venous pharmacokinetics.
BACKGROUND
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 waking, expired carbon monoxide >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 12 hr (Part 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 after the start of inhalation 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 after the start of inhalation for the 0.22, 0.45, and 0.67 mg doses, respectively. In Part C, the mean pre- and postdose venous plasma nicotine concentration increased steadily and fluctuated in the range 8-10 mg/mL after 9 hr. The novel device was well tolerated; most adverse events were mild.


CONCLUSIONS
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 sensorial aspects of smoking.
Kind Consumer Limited, London, UK; chris.moyses@kindconsumer.com.
Chris
C
Moyses
Kind Consumer Limited, London, UK;
Alex
A
Hearn
Linear Clinical Research Limited, Perth, Australia.
Andrew
A
Redfern
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D009538:Nicotine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012907:Smoking / Q000188:drug therapy*; D016540:Smoking Cessation / Q000379:methods*; D006113:United Kingdom
D009538:Nicotine