Is Amoxicillin Metabolised in the Liver? A Pharmacological Review

October 12, 2025 •

3 min read

In the United States, amoxicillin is prescribed around 50 million times each year. A common question patients and clinicians have is: is amoxicillin metabolised in the liver? The answer is that it is only partially metabolised in the liver.

Quick Summary

Amoxicillin is primarily excreted unchanged by the kidneys, not extensively metabolized by the liver. Understanding this pathway is crucial for safe drug use, especially in patients with impaired renal function.

Key Points

Primary Excretion: Amoxicillin is primarily excreted by the kidneys, with about 60% of the dose eliminated unchanged in the urine within 6-8 hours.
Liver Metabolism: The liver plays a minor role, metabolizing only about 10% of the amoxicillin dose.
Short Half-Life: Amoxicillin has a very short half-life of approximately one hour in adults with normal renal function.
Renal Impairment: Patients with severe kidney disease require careful consideration of drug use due to the kidneys' primary role in excretion.
Liver Disease: Adjustments are not typically needed for patients with liver impairment, though rare instances of liver injury have been reported.
Drug Interactions: Probenecid can delay amoxicillin's excretion by the kidneys, increasing its concentration in the blood.
Amoxicillin-Clavulanate: The combination drug (Augmentin) is a common cause of drug-induced liver injury, an effect largely attributed to the clavulanate component.

Amoxicillin's Journey Through the Body: Metabolism and Excretion

Amoxicillin, a widely used aminopenicillin antibiotic, undergoes a specific journey through the body known as its pharmacokinetic profile. A key part of this process is metabolism and excretion. While many drugs are extensively broken down (metabolized) by the liver, amoxicillin is different. It is only partially metabolized in the liver. In vitro studies using human liver microsomes have identified several metabolic processes, including oxidation, hydroxylation, and oxidative deamination. However, this hepatic metabolism accounts for only about 10% of an administered dose.

The Primary Role of the Kidneys

The vast majority of amoxicillin is eliminated from the body by the kidneys. Approximately 60% of an oral dose of amoxicillin is excreted unchanged in the urine within 6 to 8 hours of administration. Some sources even place this figure as high as 70-75%. This process occurs through both glomerular filtration and tubular secretion. The drug's half-life, which is the time it takes for half of the dose to be eliminated, is very short, at approximately 61.3 minutes (about one hour). Because of this rapid renal clearance, detectable serum levels of the drug may only last for up to 8 hours after a dose.

Implications for Patients with Liver and Kidney Disease

Because amoxicillin is not primarily dependent on the liver for elimination, dosage adjustments are generally not required for patients with hepatic impairment. Amoxicillin is considered generally well-tolerated in patients with liver conditions like fatty liver disease, unless there is significant liver dysfunction. However, it is important to note that while rare, amoxicillin can cause drug-induced liver injury (DILI). A UK study estimated that liver injury from amoxicillin alone occurs in about 0.3 cases per 10,000 prescriptions. The risk is notably higher when amoxicillin is combined with clavulanate (Augmentin), where the combination is a leading cause of DILI.

Conversely, because the kidneys do the heavy lifting of excreting amoxicillin, the risk of toxic reactions increases in patients with impaired renal function. For this reason, careful consideration of drug use is critical for patients with severe kidney disease.

Comparison of Elimination Pathways

To understand amoxicillin's profile better, it's helpful to compare it with antibiotics that are primarily metabolized by the liver.


Feature	Amoxicillin	Liver-Metabolized Antibiotics (e.g., Ciprofloxacin, Nafcillin)
Primary Organ of Elimination	Kidneys	Liver
Excreted Form	Mostly unchanged in urine (60-75%)	Metabolized into other substances before excretion
Impact of Kidney Impairment	High risk; requires significant adjustment	Lower impact on clearance
Impact of Liver Impairment	Low impact; adjustment usually not needed	High risk; may require adjustment or alternative drug

Drug Interactions

The primary route of excretion for amoxicillin also influences its drug interactions. One notable interaction is with probenecid, a medication used to treat gout. Probenecid can delay the excretion of amoxicillin by competing for the same renal tubular secretion pathway, leading to higher and more prolonged blood levels of the antibiotic. While amoxicillin-induced liver injury is rare, it can happen, and when it does, liver enzyme levels typically return to normal after the drug is stopped. The combination of amoxicillin with clavulanic acid is far more frequently associated with liver injury, which is believed to be caused by the clavulanate component.

Conclusion

To answer the question, is amoxicillin metabolised in the liver?—only to a small extent. Its pharmacological profile is dominated by rapid and substantial excretion of the unchanged drug by the kidneys. This makes it a generally safe option for individuals with liver problems but requires careful management for those with compromised kidney function. The distinction between amoxicillin alone and its combination with clavulanate is also critical, particularly concerning the risk of drug-induced liver injury.

For more detailed information on amoxicillin's pharmacology, you can visit the NCBI StatPearls article.

Frequently Asked Questions

Amoxicillin alone is a rare cause of liver injury. It is primarily cleared by the kidneys, not the liver. However, the combination of amoxicillin and clavulanic acid is a well-known cause of drug-induced liver injury.

Amoxicillin is primarily hard on the kidneys if their function is already impaired, as they are responsible for excreting the drug. For individuals with normal kidney function, it is generally safe. It is not considered hard on the liver.

Only about 10% of an amoxicillin dose is metabolized by the liver. The remaining majority is excreted unchanged by the kidneys.

No, product labeling and clinical guidelines do not typically recommend adjustments for amoxicillin in patients with hepatic (liver) impairment.

Amoxicillin is primarily removed from the body through the urine. About 60% of an oral dose is excreted unchanged by the kidneys within 6 to 8 hours.

Amoxicillin has a short half-life of about one hour. Most of the drug is gone from the body within 8 hours, and it should be completely cleared within 12 hours in a person with normal kidney function.

Unlike amoxicillin, some antibiotics are extensively metabolized by the liver. Examples include nafcillin, ciprofloxacin, and norfloxacin. The liver converts these drugs into substances that can be more easily excreted.