I’d never even given a second thought to the subject of activated charcoal until this thread. Thanks. I think.
See, that was my initial thought, but I do take BP medication, so it made me question the choice. Most likely I’d be making it to eat with smoked salmon. Might end up eating a quarter loaf or so if I’m feeling motivated. Thanks!
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Activate charcoal has a very large surface area and the amount used in hospital setting is used for immediately need in case of poison. Already significant smaller amounts of charcoal will most likely have an effect on drug concentrations in your body.
Every single one of your points is available on line. Which is where I found them before I posted the first time.
Absolutely. I am simply trying to put things in perspectives too. First of all, the first thing the activated charcoal will see is the food ingredients being baked along with it. The charcoal will interact with those first. Effectively, the food ingredients will saturates it. You are not eating activated charcoal alone. Second, you are not taking this activated charcoal day in and day out. You are eating a couple pieces of bread with small amount of activated charcoal. Third, plenty other foods have effect on drug. Classic case, grapefruit. Grapefruit can inhibit CYP3P4 which then can change the drug metabolism of a wide range of drug, so can other foods too.
Fatty foods can change drug absorption as well.
Let me say at the end. I am not promoting you put charcoal in your food. I am simply saying … in grand scheme of things… there are far more dangerous things in your recipe than that 0.5 gram of charcoal you may consume.
To use layman term, grapefruit can increase the drug concentration (inhibition of CYP3P4) or decrease the drug concentration. The former is usually far worse. Just think… what is worse? Take 10 times the drug prescribed or forgot and skipped a dose? Of course, overdose is worse.
Back to the whole activated charcoal,… first I highly doubt the small activated charcoal embedded in foods will have much effect on your drug. Second, even if you assume the worse case, that the charcoal will absorb some drug in your GI tact, then it would as if you took a half a pill instead of a full pill. You will have a lower dose, not higher dose.
I am the last person who will advocate eating charcoal as a healthy lifestyle or some kind of detoxication. However, the idea that swallowing 0.5 gram of charcoal along with the rest of your meal (one meal) will somehow hurt you is ridiculous. You have far more to worry about that Guinness and sugar you are consuming from that bread. There are wealth of evidences that alcohol effect on drug interaction. Why shouldn’t you worry about the Guinness?
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Nobody is saying that the amount of charcoal is killing you but at the same time, having to do with drug discovery and development on a daily basis as part of my job, a lot of your assumptions are way oversimplified or wrong. It will go way off topic (and is much easier discussed F2F) but just to pick one of many of your points that an accidental higher dose has automatically more negative implications than an accidental lower dose is not correct and really depends on the metabolic pathway of your drug
Of course, a higher dose is far worse than a lower dose. A single higher dose will easily put you into the toxicological drug exposure. A person can die by taking 100 times the dose prescription. You are telling people that if they take a drug that is 1/100th the intended level for one time, they will die? Tell me in which clinical trial that a person skipping one dose will die? Just name a single clinical trial. There is no drug on this Earth that a person skipping a dose will die. First, that makes no sense. The dose regiment will never allow the drug to reach C min by missing one dose. It takes at least 3 terminal half life to get to what people consider as C trough. The dose regiment will maintain a steady state and missing one dose isn’t going to make the dose exposure goes to zero. Second, clinical trials start with the lowest dose to the highest dose in the dose escalation. There is a reason why clinical trials start from low to high doses, not high to low. You do know understand this, right? Third, there is no drug put a patient in this much “dependence”. Fourth, in clinical trial, missing doses are part of trial. In fact, world health agencies FDA EMA PMDA… do not want clinical trials overly enforce subjects stay on the rigid dose regiments. For those subjects who skip a couple regiments, they are still part of the trial. Why is that? Because in real life, people do misses doses, so by accounting people missing doses in the clinical trial, then it is more reflective of the real world situation. You do know that, don’t you?
Hey, here is an idea for you… in all clinical trials, there is a beginning, and there is an end. At some points, the subjects were taken off the testing compounds. What happen to these people when they were permanently taken off the drug?
It is off topic, and you have twice written to me, so maybe you should stop being off-topic?
No, in a clinical setting a lower dose is much more likely to be detrimental to the clinical outcome. Your example of 100x overdose has nothing to do with real life examples (if we don’t talk about suicide attempts). What is a real life example in a clinical setting is that either a patient forgets at one or multiple days to take his drug or he forgot that he already took it and takes an additional dose - in both cases it is very unlikely that it will lead to immediate death but the question is which will have a higher likelihood to have a negative effect on the clinical outcome - and that is when you under-dose and don’t reach Ceff. Since you have anyway a high likelihood of significant patient to patient PK variability you tend from a drug design standpoint work in a way that your drugs don’t rely metabolically on a single pathway but on more than one so that when one pathway is saturated (if you take for example too much drug or have an unfavorable PK profile) you have others to compensate. On the other side if you don’t take enough drug there is no drug design which can be used to compensate. In addition, especially in an oncology setting more and more drug targets are sometimes going after essentially genes etc which means that you don’t want to have 24 hours AUC coverage but want the drug relatively fast cleared to get the best TI which also means that if you are not dosing high enough because you forgot to take your drug you never reach efficacy levels and your tumor grows (and there are many fast growing tumors, e.g. pancreatic, that missing a few days of drugs from time to time will increase your chance of negative clinical outcome/death much more than a few times accidentally taking the double dose.
BTW, clinical trial protocols include criteria for both cases that a patient takes a double dose or forgets one. And clinical trial design relies on strict dosing (obviously not in Ph 1 MAD study) to get a better correlation to human PK and it is only flexible when you see side effects.
Now, you avoiding and switching the discussion. Now you are talking about efficacy outcome – an interest for the pharmaceutical companies. That is not the same as drug toxicity. Of course, at lower dose, there is a higher chance of not being efficacious, but that is not the same as being toxic. At higher dose, the higher the chance of toxicity.
Again, your example avoid the fact that clinical trial always start with lower dose to higher dose. Why is that? Even for oncology, one starts lower and then adjust up. Because the guiding principal is simple. First, the drug causes no harm, and then talk about efficacy. This is also the primary end point for Phase 1. The agencies always ask to start from a lower dose. Your example of clinical outcome failure is bad for the pharmaceutical companies.
I knew you were going to use oncology. Oncology is such as special and extreme case. This is case where the disease is so aggressive and deathly that the toxicology of any overdosed are compromised. Losing hair, fingernail falling off are all acceptable side effect for oncology for saving the patient. You think having fingernail falling off is acceptable for a weight loss drug? This is also why there is no placebo group in an oncology trial. I can easily use the opposite case where the a disease is mild.
Being overexposure to a dose is a real risk, your example taking two pills is missing the picture. Overexposure can occur such as drug-drug interaction or food-drug interaction or hepatic or renal impairment…all of these can affect more than the “two fold” increase than say taking the drug twice. You are seriously underestimate the risk of drug exposure and misleading. Vast majority of the health agency stance is avoiding dose overexposure – such as start at low dose and escalating up or testing against hepatic impairment patients to see if lower metabolism leading to higher exposure is a concern. Forget to take one dose is simply as bad as the other direction. It cannot go to zero.
Since we talking about activated charcoal, please explain why a 0.5 gram charcoal baked in a middle of all kind of foods, will selectively absorb the drug compound, but not the food compounds around it?
There are hardly clinical drop outs because of overdoses because it is not that likely to have a negative clinical outcome (as you have any way significantly PK differences between patients and different levels of clearance mechanism, e.g. Cyp levels etc.) It is much more likely that a patient dropping out because of missing efficacy -either because they picked the wrong target or drugs levels couldn’t reach efficacy levels (including patients not taking their drugs)
It will absorb drug, food etc but if I would use it to bake I wouldn’t give it to somebody if I don’t know if this person takes any drugs including contraceptives -why risk that it could have an unexpected negative effect on the drug levels
Yet, there are definitely clinical withdrawal because of adverse events. In fact, it is one of the main concerns. Yes, there is always a PK difference between patients, but you are assuming there is already a healthy and wide therapeutic margin. As such, going a little higher should be ok, but so will a little lower too because a wide therapeutic compound is unlikely being administrated at the very thin border of being inefficacious at lower exposure. If a drug is designed to administrate at the barely efficacy dose/exposure, then it must have a narrow therapeutic window, and a toxicity trying to avoid.
That is your choice. Isn’t it? Someone may also have the choice of not baking/cooking with high fat content or alcohol too. Activated charcoal is not some selective target thing. It starts absorbing and binding immediately to many things next to it - which is why it is used to purify water too. You put 0.5 gram of activated charcoal in the middle of all the foods and baked it… Tell me what percentage of this activated charcoal still remain activated after interacting with the foods? Only then the person consume it. Even if there is trace of activated charcoal after, how much do you think it is interacting with the drug in the sea of all other non-therapeutic compounds in GI intact? .
I am not advocating eating charcoal on a daily basis, but we are talking about one meal. I am also not advocating people drinking alcohol every day as well. The original poster can make her own decision.
Alcohol can also change PK profile. So why are you not jumping up and down for the 500 mL of Guinness. Even regular food has an effect on PK profile. The bread itself here will have an effect too. If not elimination, then at least drug absorption. Why are you so focus on the 0.5 gram of chacoal? Why not the beer? Why not the bread itself?
That’s a constant risk-joy evaluation on everything you do in life and everybody has different preferences. I know people who think that drinking alcohol on a relatively regular basis isn’t fun enough to risk potential higher risk of certain cancers but some of them like sky-diving and think the risk on an accident in minimal - I am aware of the potential of higher cancer risk of alcohol but get enough enjoyment from a glass of beer or cocktail from time to time but you couldn’t pay me any money to sky-dive
No. I am not talking about that. I am talking about the 500 mL beer in that bread recipe. Why are you so concern of the PK effect of charcoal in the recipe, but not concern of the 500 mL beer has a PK effect?
Now, now. You are doing this again. Changing and setting the bar differently. For the charcoal, your argument is that you do not believe you have the right to give it to someone because you don’t want to risk for someone else. Yet, when it comes to alcohol, suddenly it is about the choice of the person? It is no longer about you having the right to give the alcohol to someone? Why changing the point of view so much?
I haven’t looked at the recipe at all but if it contains beer the alcohol would be evaporated once the bread comes out of an oven. If I would make a recipe which would contain significant amounts of alcohol which don’t evaporate I would definitely consider who I would serve it to and make sure that the amount of alcohol doesn’t have the potential to have negative effects on the person.
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Ok, then why are you able to rationalize that most of the ethanol would be evaporated, but not most of the charcoal being inactivated/saturated by the food ingredients for 2 hours of baking?
It is a myth that 100% of alcohol evaporates during cooking.
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Hi - I appreciate the science discussion between the two of you, since I don’t have the background. FWIW, the recipe has the dough rest overnight, so the stout, 500ml, and activated charcoal (1 tsp.) would be sitting together for 16-20 hours (per the the recipe) before another 2 hours proofing and 55 minutes baking. In case any of that makes a difference to outcome.
