What is the elimination half‑life of Augmentin (amoxicillin/clavulanic acid) in an adult with normal renal function, and how does renal impairment affect it?

Elimination Half-Life of Augmentin (Amoxicillin/Clavulanic Acid)

In adults with normal renal function, amoxicillin has an elimination half-life of approximately 1.0–1.2 hours, while clavulanic acid has a shorter half-life of approximately 0.85–1.15 hours.

Pharmacokinetics in Normal Renal Function

Amoxicillin Component

• The elimination half-life ranges from 1.05 to 1.22 hours in subjects with normal kidney function 1, 2, 3
• The drug is primarily eliminated renally, with a body clearance of approximately 0.11–0.12 L/h/kg 2
• Volume of distribution is approximately 1.77 L/kg 3

Clavulanic Acid Component

• The elimination half-life is 0.85 to 1.15 hours in normal renal function 1, 2, 3
• Body clearance is similar to amoxicillin at approximately 0.12 L/h/kg 2
• Volume of distribution is approximately 1.30 L/kg 3

Key Pharmacokinetic Principle

• Both components are eliminated independently and do not alter each other's disposition kinetics when administered together 2
• The shorter half-lives of both drugs necessitate dosing every 8–12 hours to maintain therapeutic concentrations 3

Impact of Renal Impairment

Moderate Renal Impairment (CrCl 10–35 mL/min)

• Amoxicillin half-life extends dramatically to approximately 13.6 hours (10-fold increase) 1
• Clavulanic acid half-life increases to approximately 3.05 hours (3-fold increase) 1
• The differential prolongation creates a disproportionate accumulation of amoxicillin relative to clavulanic acid 4

Severe Renal Impairment (CrCl <10 mL/min or Hemodialysis)

• Total body clearance of amoxicillin decreases more dramatically than clavulanic acid 4
• The ratio of amoxicillin to clavulanic acid area-under-curve increases from 4.9:1 in normal function to 14.7:1 in hemodialysis patients 4
• Both drugs are significantly removed by hemodialysis, with fractional removal of approximately 64% for amoxicillin and 65% for clavulanic acid during a 4-hour session 1

Critical Dosing Adjustment

• Dose reduction is mandatory in renal impairment to prevent amoxicillin accumulation while maintaining adequate clavulanic acid levels 4
• The non-renal clearance of both drugs is also reduced in end-stage renal disease, suggesting some degree of hepatic impairment in uremic patients 1

Clinical Implications

Dosing Frequency

• The short half-lives in normal renal function require administration every 8–12 hours to maintain concentrations above the minimum inhibitory concentration for susceptible pathogens 3
• In renal impairment, dosing intervals must be extended proportionally to the degree of kidney dysfunction 4

Common Pitfall to Avoid

• Do not assume equal accumulation of both components in renal failure—amoxicillin accumulates disproportionately more than clavulanic acid, which can lead to amoxicillin toxicity while clavulanic acid levels remain subtherapeutic if standard doses are used 4
• Failure to adjust for renal function can result in excessive amoxicillin exposure and increased risk of adverse effects 1