How is amoxicillin (amoxicillin) metabolized and excreted in patients with normal and impaired renal function?

Amoxicillin Metabolism and Excretion

Amoxicillin is minimally metabolized in the liver and is primarily eliminated unchanged by the kidneys, with approximately 60% of an oral dose excreted unchanged in the urine within 6 to 8 hours. 1

Metabolism

• Amoxicillin undergoes limited hepatic metabolism, with the liver serving as the probable site of inactivation 2
• The drug can be metabolized to penicilloic acids in humans, though amoxicillin shows relatively good stability compared to other penicillins 2
• In vitro studies have identified six phase I metabolites (via oxidation, hydroxylation, and oxidative deamination) and one phase II metabolite (glucuronide conjugate), though the clinical significance of these metabolites is limited given the predominant renal excretion of unchanged drug 3
• Most of the drug is excreted unchanged rather than as metabolites, distinguishing it from drugs that are primarily hepatically cleared 1

Excretion in Normal Renal Function

• The half-life of amoxicillin is 61.3 minutes in patients with normal renal function 1
• Approximately 60% of an orally administered dose is excreted unchanged in the urine within 6 to 8 hours 1
• Detectable serum levels persist up to 8 hours after oral administration 1
• Amoxicillin is approximately 20% protein-bound in blood serum, which facilitates renal clearance 1
• Concurrent administration of probenecid can delay excretion by blocking tubular secretion 1

Excretion in Impaired Renal Function

Dosing Adjustments Required

• Amoxicillin is primarily eliminated by the kidney, and dosage adjustment is usually required in patients with severe renal impairment (GFR less than 30 mL/min) 1
• The risk of toxic reactions is greater in patients with impaired renal function because amoxicillin is substantially excreted by the kidney 1
• In neonates and young infants with incompletely developed renal function, elimination of amoxicillin may be delayed, requiring dosing modifications 1

Key Principle for Renal Dosing

• Instead of decreasing the dose, increasing the dosing interval is the recommended approach to maintain adequate peak concentrations while avoiding accumulation 4
• Diminished renal function changes the volume of distribution, metabolism, rate of elimination, and bioavailability 4
• The dose adjustment should be lengthened according to the degree of elimination impairment 4

Hemodialysis Considerations

• Amoxicillin may be removed from circulation by hemodialysis 1
• High blood levels may occur more readily in patients with impaired renal function because of decreased renal clearance 1
• Adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin crystalluria in overdose situations, as crystalluria can lead to renal failure 1
• Antituberculosis guidelines suggest that drugs cleared by hemodialysis should be given after the dialysis session to avoid premature drug removal and facilitate directly observed therapy 4

Clinical Monitoring

• In elderly patients, care should be taken in dose selection and monitoring renal function may be useful, as they are more likely to have decreased renal function 1
• For patients with reduced creatinine clearance but not less than 30 mL/minute, standard doses may be used, but measurement of serum concentrations should be considered to avoid toxicity 5