Nicotine Pharmacokinetics: Comparison of a cigarette, loose snus, pouched snus and nicotine gum

Transcription

1 ST CORESTA Smoke Science/ Product Technology 9 13 October 2011 Graz, Austria Nicotine Pharmacokinetics: Comparison of a cigarette, loose, pouched and nicotine gum H. Digard a, C. Proctor a, U. Malmqvist b, A. Richter a a British American Tobacco, Group R&D, Regents Park Road, Southampton, SO15 8TL, UK b Clinical Research and Trial Centre, Lund University Hospital, SE Lund, Sweden

2 Background Swedish-style is available in pouched and loose form Consumption survey of Swedish users : - users of loose consumed a greater weight of tobacco each day than users of pouched Average systemic doses of nicotine from loose and pouched reportedly similar, based on nicotine equivalents in 24 hour urine Rate of uptake & max. plasma nicotine from intermediate between those for cigarettes and nicotine gum or dermal patches* Patterns and Behaviors of Snus Consumption In Sweden. H. Digard, et al. 2009, Nic. & Tob.Res., 11: Oral mucosal changes and nicotine disposition in users of Swedish smokeless tobacco products: a comparative study. G. Andersson, et al. (1994). J.Oral Pathol.Med., 23: *Effect of Smokeless Tobacco (Snus) on Smoking and Public Health in Sweden. J. Foulds, et al. 2003, Tob. Cont., 12:

3 Study Objective Conducted: - A randomised, pharmacokinetic study of multiple tobacco products and an OTC nicotine product in healthy subjects Study Objectives: - To investigate how product type (pouched versus loose) and nicotine content affects nicotine absorption kinetics - To compare nicotine absorption kinetics for different products against those for a cigarette and a nicotine replacement product

4 Study Details Country: Sweden (one site) Approvals: - Independent Ethics Committee - Swedish Medical Products Agency - Required due to inclusion of the nicotine gum - Trial Registration Number: ISRCTN Number of Subjects: - 20 daily users who occasionally smoke - Aged between 19 and 55 years Single Product Use Use of tobacco restrictions - Subjects asked to refrain from using tobacco or nicotine products for 12 hours prior to visit

5 Study Test Products Product Target Weight Measured Nicotine per product Cigarette NA 0.9 mg* 1g 10.8 mg 2.5g 27.1 mg 1g 10.7 mg 1g 14.7 mg Nicotine gum (Nicorette ) NA 4.2 mg *Nicotine in smoke, ISO method Total weight including that of the pouch. The five tobacco products were manufactured by British American Tobacco and commercially available in Sweden at the time of the study The nicotine gum was purchased in a Swedish pharmacy

6 Study Product Administration SNUS: - Snus portion placed under upper lip - Product used for 1 hour CIGARETTE: - Smoked naturally for 5 minutes or until cigarette had been smoked to 30mm from the filter tip end - Cigarette extinguished NICOTINE GUM: - Product used for 30 minutes - Gum chewed every 2 seconds in time with a metronome

7 Study Design One test product administered to each subject at each visit (Visits 1 to 6) - Products randomised For each visit: - Administration of product - Blood samples taken at set times for nicotine analysis - 10 samples were taken at specific times over 2 hours - An extra sample taken for the cigarette product - Samples were taken before, during and after use Analysis of nicotine in plasma was performed by LC-MS/MS

8 Nicotine Plasma concentration (ng/ml) Geometric Mean of Plasma Nicotine Concentrations Snus (27.1mg nicotine) Snus (14.7mg nicotine) Snus (10.7mg nicotine) Time post-administration (min) Nicotine Gum (4.2mg nicotine) Cigarette (0.9mg nicotine) Snus (10.8mg nicotine) --- Lower limit of quantification (0.5ng/ml)

9 Nicotine Plasma concentration (ng/ml) Median time to maximum concentration of nicotine (T max ) Snus: 60 minutes Nicotine Gum: 45 minutes Cigarette: 7 minutes Snus (27.1mg nicotine) Time post-administration (min) Cigarette (0.9mg nicotine) Snus (14.7mg nicotine) Snus (10.7mg nicotine) Snus (10.8mg nicotine) Nicotine Gum (4.2mg nicotine) --- Lower limit of quantification (0.5ng/ml)

10 Summary of PK Parameters for Nicotine Cigarette (0.9 mg) (10.8 mg) (27.1 mg) (10.7 mg) (14.7 mg) Nicotine gum (4.2 mg) AUC ng.h/ml Geometric Mean* CV% C max ng/ml Geometric Mean* CV% t max h Median* Range: min,max *N = , , , , , , 1.50

11 and Snus with the same nicotine content Cigarette (0.9 mg) (10.8 mg) (27.1 mg) (10.7 mg) (14.7 mg) Nicotine gum (4.2 mg) AUC ng.h/ml Geometric Mean C max ng/ml Geometric Mean t max h Median Systemic nicotine exposure is similar for loose and pouched products with approximately the same nicotine content

12 Systemic nicotine exposure increased with increasing nicotine content Nicotine mg Cigarette Nicotine gum AUC ng.h/ml The highest exposures were seen for the products with the highest nicotine contents C max ng/ml This increase appeared to be smaller than the increase in nicotine content for both types of Nicotine content increment Measured Nicotine Content Snus Snus 27.1 mg 14.7 mg Increase in AUC 0-tlast Increase in C max

13 Systemic Exposure of Tobacco Products compared to the Nicotine Gum Cigarette (0.9 mg) (10.8 mg) (27.1 mg) (10.7 mg) (14.7 mg) Nicotine gum (4.2 mg) AUC ng.h/ml Geometric Mean C max ng/ml Geometric Mean t max h Median All of the tobacco products gave higher systemic nicotine exposure than the nicotine gum

14 Summary The nicotine exposure was similar for the 10.7mg nicotine pouched compared to the 10.8mg loose portions, suggesting that product form had no effect on the absorption kinetics of nicotine Systemic nicotine exposure increased with increasing nicotine content for both types of, although increases in exposure were sub-proportional to the increases in nicotine content All of the tobacco products gave higher systemic nicotine exposure than the nicotine gum

15 Acknowledgements The authors thank the following for invaluable input and assistance: - Graham Errington, Karsta Luettich, Oscar Camacho and Nathan Gale of GR&D, British American Tobacco - Covance Clinical Research Unit, Leeds, U.K. - Fiedler & Lundgren, Malmo, Sweden - British American Tobacco Regional Product Centre Europe, Bayreuth, Germany Thank you for Listening Any questions This presentation is available on bat-science.com