Do compounds absorbed through the skin bypass the liver?
A friend of mine posted this on social media:
90% of what you put into your mouth is detoxed by your liver. What you put on your skin bypasses liver detoxification.
They mentioned that there was a study that confirmed this, but didn't link to it.
Is there any research that can back up this claim? It seemed strange to me - wouldn't anything in the bloodstream eventually get filtered through the liver?
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No. We'll go through two examples of why not.
Dermal application of medicine. If the main goal of this is to get the medicine circulating in your blood for systemic applications, and the drug is absorbed well through the skin, then the skin route will provide a stronger effect, for a short time. Why? Because the liver metabolizes anything that's entered your bloodstream. No matter how it got there (orally, dermally, rectally).
Alcohol. If you inject alcohol, it will affect you much, much more quickly than if you took it like any normal person would. But remember, it's in your bloodstream. Your liver WILL eventually process it, but it might have a harder time because it's entered your bloodstream much faster than if it had had to have entered through your mouth and stomach first.
It seems that your friend has confused first-pass metabolism with overall liver metabolism. Anything that goes into your digestive tract (including the medicines taken (per)orally) goes straight to the liver, through hepatic portal vein. Once the substances reach the liver they are metabolised to a certain extent, depending on their chemical structure. Then, blood is carried from the liver by hepatic veins to vena cava inferior which leads to the right atrium of the heart. The heart pumps the blood into the whole body (including the liver) and substances in the blood go round and round being metabolised in each turn.
If a substance enters the body in any way other than the digestive system, it gets to the heart and goes round and round through the whole body, including the liver and each time it passes the liver gets metabolised. The thing is that the substances reach the heart and enter systemic circulation before they reach the liver - the first pass effect is bypassed.
Hence, I can't find research that supports your friend's wrong claim, but there are plenty of resources that refute it. For instance:
Although the plasma concentration-time profiles of metabolites may differ after oral and parenteral doses, the fraction of a dose eventually converted to a metabolite should be the same after each route of administration provided that the ingested drug is completely absorbed, is eliminated solely by metabolism in the liver, and has linear kinetics. Otherwise, the fraction of a dose administered that is converted to a metabolite may vary with route of administration (e.g. with isoprenaline and salbutamol).
from: Susan M. PondThomas N. Tozer, First-Pass Elimination Basic Concepts and Clinical Consequences, Clinical Pharmacokinetics, 1984
A clinically significant aside: medicines that show extensive first pass metabolism sometimes cannot be used perorally. This is a case with nitroglycerin, e.g. This is why it is often used sublingually, i.e the tablet is placed under the tongue, but should not be swallowed. This way the first-pass metabolism is bypassed, but the medicine is still extensively metabolised by the liver, as soon as it reaches it. There are also intravenous and transdermal forms, but the sublingual form is interesting because although it is something you "put into your mouth" the effect your friend is talking about is bypassed.
Glyceryl Trinitrate Tablets 500 micrograms SmPC
Nitroglycerin pharmacokinetics
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