Half-Life of Amoxicillin in Augmentin 875/125 mg
The half-life of amoxicillin in the 875/125 mg formulation of Augmentin is approximately 61 minutes (approximately 1 hour), while clavulanic acid has a slightly shorter half-life of approximately 1.03 hours. 1
Pharmacokinetic Profile
Amoxicillin demonstrates a terminal half-life of 61.3 minutes following oral administration, which is consistent across different formulations including the 875/125 mg dose 1
Clavulanic acid has a terminal half-life ranging from 1.03 to 1.27 hours, which is similar to amoxicillin but slightly variable depending on the specific study 2, 3
Peak serum concentrations of amoxicillin occur at approximately 1-2 hours after administration, with the 875 mg dose producing a mean Cmax of 13.8 ± 4.1 mcg/mL and an AUC of 35.4 ± 8.1 mcg•hr/mL 1
Peak serum levels for clavulanic acid occur slightly earlier at approximately 1 hour, reaching concentrations of 2.55 ± 0.54 mcg/mL after the 875/125 mg dose 4
Clinical Implications of the Short Half-Life
The short half-life of both components necessitates twice-daily dosing for the 875/125 mg formulation to maintain adequate therapeutic concentrations 5, 6
Approximately 60% of amoxicillin is excreted unchanged in the urine within 6-8 hours, and detectable serum levels persist up to 8 hours after oral administration 1
Beta-lactam antibiotics like amoxicillin demonstrate time-dependent killing with only a brief post-antibiotic effect, meaning they require frequent dosing to maintain concentrations above the minimum inhibitory concentration (MIC) for optimal bacterial eradication 7
By 12 hours after dosing, plasma amoxicillin concentrations drop to very low levels (approximately 0.05 mcg/mL), which supports the twice-daily dosing regimen without significant dose-to-dose accumulation 2
Dosing Considerations Based on Half-Life
The 875/125 mg formulation is specifically designed for twice-daily administration to compensate for the short half-life while providing adequate coverage for respiratory infections, skin and soft tissue infections, and other moderate-to-severe bacterial infections 5, 6
For optimal pharmacodynamic effect, the time above MIC (T>MIC) should exceed 40-50% of the dosing interval, which the 875/125 mg twice-daily regimen achieves for most susceptible organisms 8, 2
Pharmacokinetically enhanced formulations (such as 2000/125 mg extended-release) were developed to extend the T>MIC to approximately 49-79% of the dosing interval, addressing the limitation of the short half-life for organisms with higher MICs 8, 2
Special Populations
In patients with end-stage renal disease on hemodialysis, the half-life of amoxicillin extends dramatically to 13.6 hours on non-dialysis days, requiring significant dose adjustment 3
During hemodialysis, the half-life decreases to 2.30 hours for amoxicillin and 1.19 hours for clavulanic acid, with approximately 64-65% of both drugs removed during a 4-hour dialysis session 3