From the Guidelines
Glucocorticoids undergo significant first-pass metabolism in the liver, with approximately 90% of orally administered budesonide being metabolized, as seen in a study published in the journal Gut 1. When taken orally, glucocorticoids like budesonide are absorbed from the gastrointestinal tract and transported via the portal circulation to the liver before reaching systemic circulation.
- In the liver, enzymes primarily from the cytochrome P450 family metabolize these compounds, converting them to less active or inactive metabolites.
- This process significantly reduces the amount of active drug that reaches the systemic circulation, with bioavailability varying among different glucocorticoids.
- For example, budesonide has a 90% first-pass metabolism in the liver, although in patients with cirrhosis with shunts, the metabolism may be variable, as noted in a study published in Gut 1.
- The first-pass effect explains why oral doses of glucocorticoids are typically higher than parenteral doses to achieve equivalent therapeutic effects.
- Clinicians should consider this when switching between administration routes, as intravenous administration bypasses this first-pass effect, resulting in higher systemic drug concentrations with the same dose.
- The significant first-pass metabolism of glucocorticoids like budesonide highlights the importance of considering the route of administration and potential liver function when prescribing these medications, as supported by the study in Gut 1.
From the FDA Drug Label
Prednisolone is rapidly and well absorbed from the gastrointestinal tract following oral administration... It is metabolized mainly in the liver and excreted in the urine as sulfate and glucuronide conjugates.
The first-pass metabolism of glucocorticoids, such as prednisolone, occurs mainly in the liver. This means that a significant portion of the drug is metabolized by the liver before it reaches systemic circulation.
- Key points:
- Rapid absorption from the gastrointestinal tract
- Metabolized mainly in the liver
- Excreted in the urine as sulfate and glucuronide conjugates 2
From the Research
First-Pass Metabolism of Glucocorticoids
The first-pass metabolism of glucocorticoids, such as prednisolone, occurs in the liver and gastrointestinal tract.
- The liver is the primary site of first-pass metabolism for many drugs, including glucocorticoids 3.
- The gastrointestinal tract, particularly the intestinal mucosa, can also play a significant role in the first-pass metabolism of certain drugs, including glucocorticoids 4.
Factors Affecting First-Pass Metabolism
Several factors can influence the extent of first-pass metabolism, including:
- Enzyme activity: The level of enzyme activity in the liver and intestinal mucosa can affect the rate of drug metabolism 3.
- Plasma protein binding: The binding of drugs to plasma proteins can affect their availability for metabolism 3, 5.
- Blood flow: The rate of blood flow to the liver and intestinal mucosa can influence the extent of first-pass metabolism 3.
Specific Glucocorticoids
Different glucocorticoids may undergo varying degrees of first-pass metabolism. For example: