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First Pass Metabolism: Understanding the Basics – HealthifyMe

Written by hana

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

As a result, the concentration of the drug drops significantly before it enters the systemic circulation when one ingests it orally.

To find out why and how only a small part of the dose of tablets that pass through the digestive tract reaches the target organ in the human body, read this article.

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

Thus, it is essential to understand the therapeutic effect or toxicity of a drug to predict variation in drug response and clearance due to metabolism among individuals.

Oral administration of the drug requires passage from the colon to the liver before reaching the general circulation, which is in contrast to intravenous, intramuscular, sublingual, or transcutaneous administration. Thus, before reaching the tissues, a large portion of the dose for many drugs is reduced by metabolism.

First pass metabolism, also known as first pass effect, refers to the combined effect of metabolism by the liver and intestines where certain drugs are digested by the intestinal flora or digestive enzymes.

Track track after oral drug administration

Oral medications are adjusted by enzymes, pH, and gastrointestinal motility before being administered through the portal vein.

The portal vein is the vein that carries blood from the digestive tract to the liver. In addition, the portal vein helps the arteries supply the intestines with oxygen and blood.

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

The drug in the blood is released into the hepatic vein after passing through the sinusoids, which return deoxygenated blood from the liver back to the heart. The drug will eventually travel from the heart through the lungs into the systemic circulation.

HealthifyMe note

One way to mitigate the metabolic effects of the first pass is to deliver the drug intravenously. Another way to do this is to deliver the medication rectally. However, the effect of the first pass is not always undesirable. In some cases, it may be beneficial for the liver to biotransform the drug. These types of drugs are known as “prodrugs.” They switch from an inactive state to an active state. For example, codeine is supplied before it is biotransformed into morphine in the liver.

First pass metabolism has many health implications because a significant amount of the drug that is absorbed before reaching the bloodstream may be lost due to ‘biotransformation’ in the stomach, intestines, liver, or lungs, as described above.

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

Helps understand responses to medications.

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

Each individual has a different level of Phase I metabolism, which helps explain why patients respond to medications differently and why some patients are more likely than others to have adverse drug reactions.

Reduces drug bioavailability

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

One may change the method of administration or increase the dose to overcome this problem. With intravenous administration, the liver is bypassed, so a smaller dose is usually needed.

Helps in the proper administration of medications.

The first pass effect is important for drugs such as morphine. These medications must be taken in larger amounts by mouth because the body digests them quickly when taken orally.

Therefore, correct delivery and ongoing maintenance of drug therapy depends on understanding the clinical significance of the first-pass effect.


One of the things that can make a drug’s response differ from person to person is the first-pass effect. This occurs when the liver breaks down the drug before it can reach the bloodstream.

Some people’s livers do this more than others. If a person’s first-pass metabolism is severe, a different route of administration or a higher dose may be necessary to avoid a first-pass effect.

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

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