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First Pass Metabolism: Understanding The Basics- HealthifyMe


First Pass Metabolism: Understanding The Basics- HealthifyMe


Have you ever wondered how your body breaks down the chemicals in medicine when you take them orally? Drug metabolism has a mechanism known as the first-pass effect.

As a result, a drug’s concentration significantly lowers before it enters the systemic circulation when one takes them orally.

To learn why and how only a tiny portion of the dosage of tablets that pass through your digestive system reaches the human body’s target organ, read this article.

The primary purpose of metabolism in the human body is to change the chemical composition of consumed substances so that the body can absorb the necessary elements and get rid of the rest. Therefore, a drug’s effectiveness can increase or decrease due to metabolism, impacting an individual’s health.

Consequently, it is essential to comprehend a drug’s therapeutic effect or toxicity to predict the variation in medication response and removal caused by metabolism among individuals.

Oral drug administration requires passage from the colon to the liver before reaching the general circulation, which is contrary to intravenous, intramuscular, sublingual, or transdermal administration. Thus, before reaching the tissues, a large portion of the dose for many medicines is lowered by metabolism.

First-pass metabolism, also known as the first-pass effect, refers to the combined impact of metabolism by the liver and the gut as some medications are digested by gut flora or digestive enzymes.

Tracing the Pathway After A Drug’s Oral Administration

Oral medications are modified by enzymes, pH, and the motility of the stomach and intestine before they are administered through the portal vein.

The portal vein is a vein that transports blood from the gastrointestinal tract to the liver. In addition, the portal vein helps the arteries supply the intestine with oxygen and blood.

The sinusoids of the liver, where blood can flow, absorb medicine so that the hepatic artery can carry it to the liver cells. The hepatic artery is the artery that carries oxygen to the liver.

The medication in the blood is released into the hepatic vein after passing through the sinusoids, which return deoxygenated blood from the liver to the heart. The medicine will ultimately go from the heart through the two lungs and into the systemic circulation.

The HealthifyMe Note

One way to mitigate the effects of first-pass metabolism is to deliver the medication intravenously. Another way to do this is to deliver the medication rectally. The first-pass effect is not always undesirable, though. In some cases, it can be beneficial for the liver to biotransform the medication. These types of medications are known as “prodrugs.” They change from an inactive to an active state. For example, codeine is supplied before being bio-transformed into morphine in the liver.

First-pass metabolism has several health implications because a sizable amount of the drug quantity that is absorbed may be lost before reaching the bloodstream due to “biotransformation” in the stomach, intestine, liver, or lungs, as illustrated above.

In other words, the drug’s bioavailability significantly decreases during this initial passage through many organs.

It helps Understand Drug Responses.

According to research, patients must remain within the correct dosage of the appropriate medication. Furthermore, pharmacological dosing should take into account regular changes in human metabolism.

Each individual has a different first-pass metabolism level, which helps explain why patients respond to medications differently and why some patients are more likely than others to experience adverse drug reactions.

Lowers Drug Bioavailability

If a medication has high first-pass metabolisms, the liver breaks it down before reaching the rest of the body. As a result, it limits the bioavailability of the drug or how much of it gets into the bloodstream.

One can change the administration method or increase the dosage to get around this issue. With intravenous administration, the liver is bypassed, so a smaller dose is typically needed.

It helps in the Proper Administration Of Drugs.

The first-pass effect is significant for medications like morphine. These medications must be taken in larger quantities orally because the body digests them quickly when taken orally.

Therefore, the correct delivery and ongoing maintenance of drug treatment depend on understanding the clinical importance of the first-pass effect.


One of the things that can make drug response vary from person to person is the first-pass effect. That is when the liver breaks down a drug before it can get into the bloodstream.

Some people’s livers do this more than others. If a person’s first-pass metabolism is severe, it might be necessary to use a different method of administration or give a higher dosage to avoid the first-pass effect.

Your healthcare provider will decide what is best for you based on your medical history and your body’s needs.

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