Stephanie Root College of Pharmacy, Duluth campus. Mentor: Michael Kotlyar, PharmD.

Transcription

1 Pharmacokinetics and Acceptability of two new smokeless tobacco products Stephanie Root College of Pharmacy, Duluth campus Mentor: Michael Kotlyar, PharmD.

2 Reynolds Makes Big Move Into Smokeless Tobacco TIM WHITMIRE Associated Press June 11, 2006 (CHARLOTTE, N.C.) - Reynolds American Inc., the nation's second-largest cigarette maker, said its first-quarter profit rose 23 percent and it is planning a second major push into the smokeless tobacco category with a snuff product under its famous Camel brand. Philip Morris USA to unveil smokeless Marlboro product By Danny King and Chris Burritt Bloomberg News Published: June 11, 2007 LOS ANGELES: Philip Morris USA plans to unveil a new, spitless, smokeless tobacco product under the Marlboro brand name in an effort to spur sales as cigarette consumption declines. Smokeless Tobacco All Fired Up Convenience Store News July 16, 2007 NEW YORK -- Two major cigarette manufacturers -- R.J. Reynolds and Philip Morris -- are expanding their presence in the smokeless tobacco category.

3 Definitions Smokeless Tobacco (SLT): Encompasses both moist and dry snuff ( dipping tobacco ), sniffed tobacco, and chewing tobacco Snus: originally from Sweden, it is a moist dipping tobacco product - Can be either loose or prepackaged

4 Smokeless Tobacco Use in the U.S. From : smokeless tobacco use dropped by 37% from 2.3% in 1992 to 1.5% in 2001/2002 From self-reported data from the 2005 National Health Interview Study (NHIS), 2.3% of U.S. adults used smokeless tobacco

5 U.S. Tobacco Use using the 2005 NHIS data Smokers (20.9%) Cigar Users (2.2%) Smokeless Tobacco Users (2.3%) Non-tobacco users (74.6%)

6 Potential Reduced Exposure Products (PREPs) Institute of Medicine definition: Harm reduction by lowering toxicant exposure to user Purpose is to make tobacco use safer

7 What makes smokeless tobacco different from cigarettes? Usually more favorable lipid profile than smokers, other studies suggest snuff does not activate inflammatory processes, antioxidant consumption, or hemoconcentration as smoking does Gingival recessions that can be irreversible, oral lesions

8 Copenhagen Moist snuff Among all SLT, has one of the highest % of unprotonated nicotine Fermented tobacco

9 Commit lozenge Medicinal or pharmaceutical nicotine Used to help quit smoking Cherry and mint flavor 2mg and 4mg strengths available

10 Camel Snus Original, frost and spice flavors Spit less Test-marketed in TX and OR, and expanding to to FL, NC, OH, and KY this summer

11 Marlboro Taboka Original and menthol flavor Spit less Designed for adult smokers interested in tobacco alternatives to smoking Still in test market stage in Indianapolis Marlboro may be switching to another SLT product to market: Marlboro Snus

12 Study Objective To compare nicotine pharmacokinetics and subjective effects of two new smokeless tobacco potential reduced exposure products (PREPs) with moist snuff (Copenhagen) and medicinal nicotine (Commit lozenge)

13 What does this study add? New smokeless tobacco products emerging into the marketplace have little information regarding nicotine pharmacokinetics, or their effects on withdrawal, nicotine craving, or product effects and liking

14 Study Design 10 subjects Randomized crossover design Subject used one product for 30 min. (Camel Snus, Marlboro Taboka, Copenhagen, or Commit lozenge) at each of the four sessions. Order of product use was randomized using Latin Squares Blood draws and subjective measures

15 Summary of Protocol Total of four visits, lasting about 4 hours each Before each session: Subjects were asked to abstain from nicotine and alcohol for 12 hours before the session During each session: Additional 2 hour nicotine/caffeine abstinent period (time -120 minutes, with iv insertion and caffeine-free meal given at time -31 minutes) Product use and blood collection started at time 0

16 Summary of Protocol Product use and blood collection phase: At time 0, product is placed into subject s mouth for 30 min. Computer surveys were completed at time 0, 5 minutes, 15 minutes, and 30 minutes Blood pressure and blood collection occurred at time 0, 2.5, 5, 7.5, 10, 15, 20, 25, 30, 45, and 90 minutes Adverse drug reaction questionnaire was read to the subject at 5, 15, 30, and 45 minutes

17 Blood Samples Blood was drawn to determine plasma nicotine concentrations, epinephrine, norepinephrine, and cortisol concentrations.

18 Drug effects, liking and craving questionnaire (Baseline, 5, 15, and 30 min.) Drug effects scale (1=not at all, 10=extremely) Asks subject if they feel or have: alert; relaxed; a head rush; fast/pounding heart; tremor in hands, arms or face; lightheaded/dizzy; drowsy; energetic; jittery or high Drug liking scale (1=not at all, 10= extremely) Asks subject if the study product: reduces their craving, if they feel any good or bad effects, if it is satisfying, how much they like and desire the product, and how strong the product is Withdrawal symptoms scale (1=none, 4=severe) Asks subject if they have: a craving for tobacco; irritability, frustration, or anger; anxiety/tension; difficulty concentrating; restlessness; depressed or sad mood; impatience Also asks how confident the subject is to resist strong urges to use tobacco (1=not at all confident, 4=very confident)

19 Adverse events questionnaire (asked at 5, 15, 30 and 45 minutes) This is asked by the study coordinator Both severity and cause are asked of subject (severity scale 1=absent, 4=severe; cause scale 1=definitely related to study product, 4=unknown) Adverse events that could occur from study products: dry mouth, headaches, tachycardia, palpitations, dizziness, lightheadedness, tremor in arms, hands, or face, vomiting, nausea, stomach aches, shakiness, sore jaw or jaw pain, increased salivation, belching, hiccups, throat irritation, sore throat, mouth irritation, mouth sores, anxiety, muscle aches

20 Study Design To assure primary nicotine form was smokeless tobacco, an expired CO level was obtained from the subject at each visit Non-smokers: 1-2 ppm Current smokers: >10 ppm

21 Inclusion criteria Healthy SLT user between years Did not smoke >3 days/week Used >3 dips/day of Copenhagen Regular user of Copenhagen for >1 year No plans to quit using smokeless tobacco for the next 90 days

22 Exclusion criteria Health Conditions: Uncontrolled hypertension, active ulcers, mouth/oral disease or problems, unstable psychiatric or emotional problems Medications: taking medications / drugs likely to interact with the products being tested Drug/Alcohol use: history of drug or alcohol abuse within the past year Other: unable to tolerate wintergreen flavor, problems with having blood drawn several times, using any other nicotine or tobacco products

23 Recruitment Flyers placed around campus and surrounding area Online ad on Craig s List Newspaper ad in City Pages

24 Compensation $50 for each session, and $100 bonus for completing all four sessions and complying with the study requirements A check was sent out 2-3 weeks after study completion

25 Study Progress At least 20 phone screenings completed Three subjects had also enrolled, but were dropped either at or after their first visit due to an undisclosed regular smoking habit One subject completed

26 Experiences with the study A subject that does not smoke and uses Copenhagen only consistently is hard to find Getting subjects to show up to sessions is also a challenge

27 Questions??