Welcome to the Science Lab session hosted by Karin Jacobson from JTI Geneva. In this presentation, Anna Masser from Swedish Match discusses nicotine content and nicotine uptake in cigarettes and nicotine pouches, comparing their delivery methods, uptake rates, and how they are used both in clinical settings and real life.
The video covers:
- Differences between nicotine delivery in cigarettes vs. nicotine pouches
- Standardized clinical testing protocols for nicotine uptake
- Pharmacokinetic profiles and plasma nicotine concentration over time
- Real-world use comparison of nicotine pouches and cigarettes
- Insights into nicotine metabolism and cotinine levels
- Discussion on regulated nicotine limits and product risk profiles
- Audience Q&A addressing nicotine kinetics and product comparisons
Transcription:
00:06 - 01:10
[Karin Jacobson]
So hi, everyone, and welcome to our first science lab session of today. My name is Karin Jacobson. I work for JTI in Geneva, Switzerland, and I will be hosting this session. So we're joined here by our five speakers, and they will present and discuss their work. We will start, each speaker will get 15 minutes, and we will start by watching their GFN5 submission, so it's a five-minute video, and then we will open the floors for questions or comments. We will have microphones circulating, so after the video, if you have any questions, just raise your hand and we will get the microphone to you. And with that, we will move to our first speaker, Anna Masser. She works as a scientific writer in the product science group at Swedish Match. And in this role, Anna focuses on scientific publishing and aiming to make the company science understandable for everyone. The title of our presentation is Nicotine Content and Nicotine Uptake.
01:20 - 06:03
[Video]
This presentation will focus on nicotine content and nicotine uptake when cigarettes and nicotine pouches are used either in a standardized way or as desired. Nicotine is what cigarettes and nicotine pouches have in common. In terms of risk, they are very different because no combustion products are formed during nicotine pouch use. A cigarette does not contain one milligram of nicotine, but around 10 milligram. Nicotine pouches are all smoke-free products that contain synthetic or tobacco-derived nicotine, but no tobacco leaf or stem. They come in different strength and sizes. The German Federal Institute for Risk Assessment performed several studies on nicotine pouches. Based on their findings, they recommended an upper limit of 16.6 mg. In a smoke machine, Using the ISA method, a cigarette is allowed to emit 1 mg of nicotine, according to the EU Tobacco Products Directive. There is no smoking machine for nicotine pouches. The suggested method by some regulatory bodies is to use dissolution, where a pouch is placed in a small container with liquid. This method often overestimates nicotine release from pouches. A better way to estimate nicotine release from a pouch is to do it in a clinical setting where participants use a pouch in a standardized way. This includes how and where to place the pouch. Typically, no manipulation of the pouch is allowed during use and no eating or talking. The usage time is fixed, usually 20, 30 or 60 minutes. Before, during and after use, repeated blood samples are taken to plot the pharmacokinetic curve of plasma nicotine concentrations over time. Doing this allows for calculations of maximum plasma concentration, time to maximum plasma concentration, and total nicotine uptake, which is the area under the curve. By collecting used pouches, measuring how much nicotine that is left in the pouch, and then compare that to the average content of several unused pouches, the nicotine extracted during use can be calculated. This is how a plasma curve can look like in a single dose administration study. The cigarette was smoked with 10 inhalations taken at approximately 30 second intervals. The nicotine pouches were of the same type with varying nicotine strength. As you can see, a cigarette deliver nicotine quickly, but is finished after five minutes. There's no natural end to a nicotine pouch. Here the fixed usage time was 60 minutes, which is long. What we can see here is that independent of product, the maximum plasma nicotine concentrations are reached around product removal. So when you stop using the product, nicotine delivery also stops. Another thing is that pouch use can result in similar plasma nicotine concentrations as cigarette use, but it takes longer time. Since it takes longer time to reach the same concentration, the area under the curve will be larger. More nicotine has been taken up. illustrated in the table showing extracted amounts and fractions. Even though the pouches were used for 60 minutes, up to half of the nicotine is still left in the discarded pouch. So with slower nicotine delivery, a product requires more nicotine than a faster product to reach the same plasma nicotine concentrations. Now we move away from the clinic and standardized use to exclusive users of either cigarettes or nicotine pouches that use their products as they wanted for two weeks while they live their usual life. Then they came to the clinic to have their blood drawn. The pouch users shows pouches containing between 3 to 12.5 mg nicotine and use an average 10.7 pouches per day. Cigarette users use an average 12.2 cigarettes per day. These two groups had similar plasma nicotine concentrations. Based on the previous slide, we know that nicotine delivery with a pouch is slower, so more nicotine is required to reach the same plasma concentrations as a smoker. 70 to 80% of the nicotine is metabolized to cotinine, a metabolite with almost no pharmacological effect, and it is here that we see the difference. The pouch users have taken up more nicotine, That didn't mean that their plasma concentrations were higher. It's just an effect of choosing a slower product. Nicotine content is not nicotine uptake and a product with slow nicotine delivery requires more nicotine to achieve the same plasma nicotine concentration as a product with faster delivery.
06:04 - 06:12
[Karin Jacobson]
So I thought before we open the floor for questions, I just wanted to pass the word to Joanna, if you have, there's anything else you would like to add or comment.
06:14 - 09:41
[Video]
Yeah, I mean, maybe this was a lot for some of you, and for some of you, you already know this, but I think if we start from the back, where the participants in our study were allowed to use the products how they wanted, how many, for how long they wanted, just like you would do in your normal life, and then when they came to the clinic, to have their blood drawn, they have both nicotine pouch users and cigarette users had the same nicotine concentrations. And I didn't show the data here, but we also had snus users that only used snus. And they also, there were no significant difference in nicotine concentrations between these three groups. So I think it says something about nicotine use independent of what product you use. And of course, this is just a snapshot. We only measured this once. And since they're groups of people, of course, they exist on a normal distribution. But I found it very interesting. And I also came across a published research proposal where some scientists suggested that these glucose monitors that people with diabetes use to monitor their glucose levels in the blood, imagine if we could get that for nicotine. Then we could really learn something about concentrations and how people use nicotine. And then we had the cotinine levels. And I think this is what you see in historical publications. There are several cases where they report that smokeless tobacco users have higher cotinine levels. And when you think about the slower delivery from oral products, and that this cotinine is more stable than nicotine. It has a much longer half-life, so it kind of accumulates. So higher cotinine level doesn't really have to mean that you walk around with higher nicotine concentrations in your body. It's just that they accumulate. So this was a part of a... Often when you compare products, like different products, pouches to cigarettes, a lot of the discussion tends to be around the labeled nicotine. Now we don't have them on cigarette packs, but they're very visible on nicotine pouches. It tends to be compared like, oh, one cigarette is this many pouches. It's a very strange discussion. That's why I wanted to show this data to show that maybe it's not how much nicotine you consume, but what concentrations you end up in the body. And that a lot of the nicotine in the pouch stays in the pouch.
09:45 - 09:49
[Karin Jacobson]
Thank you, Anna. Do we have any questions from the audience?
09:51 - 10:38
[Todd Prochnau]
Hi, my name's Todd. I'm a pharmacist from Canada. I'm so happy that you shared that data because I feel like all the kinetics I've seen on pouches have always been like single use in the lab. So it's really valuable to see what people are actually, you know, real world use, like you said. And I think You know, people are really good at self-regulating their nicotine intake, regardless of how they're using it. And that really reinforces that, especially with sharing the snooze info. My question was, have you or have you considered comparing the pouch, like real-world use, to other forms of oral nicotine, so like conventional nicotine replacement therapy?
10:38 - 11:34
[Video]
It would be interesting to do. I'm not in charge of that. I'm not in charge of deciding. But I mean, it would definitely, I mean, this is what we need to learn, right? What concentrations are people aiming for? I think it's more that, I mean, in general, we tend to feel differences when something happens. I mean, you go for a swim in the 26 degree pool, and then you move to the 28 degree pool. And you feel such a shift. It feels super warm. But after a while, you don't feel it anymore. So I think it's this, we're good at feeling changes. So yeah, no. It would be cool to have such a study. It would, definitely.
11:34 - 11:40
[Karin Jacobson]
I think we have time for one more question in the back.
11:45 - 12:06
[Christoph Neubert]
Yeah, Christoph from PMI Germany. I have a question with regards to your ad libitum experimental setup. So did you control for the last time the participants used the nicotine product before checking in into the clinic? Or didn't you control for that? And then out of curiosity in the lab setup, why no speaking?
12:09 - 13:24
[Video]
Ah, so the no speaking is, I mean, mouth movement will probably affect your saliva production. And we wouldn't want that. So in the clinic, people are very still. And they're just on their beds. It's just to try to standardize. It's very difficult to standardize in people, because people are very different. And your second question, did we control if they had used just before they came in? No, because they were free to use everything as they wanted. Maybe the pouch user had a pouch in when they came to the clinic. Maybe the smoker had a cigarette just before going in. So we didn't. So that's why I said it's just a snapshot. We also checked the urine. And it correlates pretty well with the plasma. And that's more that nicotine's been already excreted.
13:29 - 13:36
[Karin Jacobson]
Thank you. So we do have time for one final question. I believe there was one here in the front.
13:37 - 14:31
[George Cassels-Smith]
George, we know that the actual nicotine content of the cigarette is about 2.5%, but that the consumer probably only gets half of that because part is bonded and the other part can be liberated. And the lung is great for absorption. Obviously, when you start talking about an oral product, You're talking about an absorption that's not deep lung, but essentially the buccal. But you also have swallowing, and the stomach is probably the third as far as efficiency in absorption of nicotine. So you're not always getting the stated nicotine amount, but did you take into account that... that the oral product user might be swallowing frequently and then not getting the full extent of the absorption of that nicotine and see efficiency.
14:32 - 15:29
[Video]
So that's the beauty of measuring how much nicotine is left in the pouch afterwards, is that you, based on the area under the curve, can back calculate to see how many milligrams that corresponds to. And you have like the answer in what's left in the pouch. So you can see how much those two correlate. And to our knowledge, it correlates very well, which would indicate that there is not so much swallowing. But I have seen in studies from other people that if you would monitor, because we usually monitor for six hours, so you would have like the initial usage peak. And then if there's a lot of swallowing, you would see like a small secondary peak But as far as I know, there's not so much swallowing that we have to account for here.
15:32 - 15:39
[Karin Jacobson]
Thank you. So thank you, Anna, and thank you for all the questions. And we then move on to our next speaker.