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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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  • We can't really prove there are no research to back up this claim. And you already know it's bogus.
    – Agent_L
    Commented Jun 7, 2016 at 17:26

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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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yes and no. oral Estrogen is metabolized thru first pass metabolism. Standard of care is to provide dermal products, which protect the liver in those with elevated liver enzymes for example. Skin application of estrogen helps to prevent overworking a partially damaged liver.

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    Hi, welcome to Medical Sciences. Answers here are required to show supporting references for claims of fact. It doesn't need to be extensive, but a link or two supporting your main points would be appropriate. Without such references, your answer may be deleted.
    – Carey Gregory
    Commented Aug 25 at 2:39
  • Hi Molly! I'd like to learn more about this, as it's new to me. Can't systemic drugs delivered transdermally still be metabolized by the liver? This is true for NTG (both transdermal and sublingual); the sublingual route bypasses the liver first pass metabolism (I see Lucky said the same thing above...) but it is still metabolized by the liver (next pass). The only dermally delivered drugs I could find that don't undergo liver metabolism are those that treat dermal conditions, so localized skin conditions. A reference would be much appreciated. Thanks. Commented Aug 25 at 5:57

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