Amoxicillin-clavulanate potassium clinical pharmacology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamed Moubarak, M.D. [2]
Clinical Ppharmacology
Mean amoxicillin and clavulanate potassium pharmacokinetic parameters in normal adults following administration of AUGMENTIN Tablets are shown in Table 3 and following administration of AUGMENTIN Powder for Oral Suspension and Chewable Tablets are shown in Table 4.
Oral administration of 5 mL of 250 mg/5 mL suspension of AUGMENTIN or the equivalent dose of 10 mL of 125 mg/5 mL suspension of AUGMENTIN provides average peak serum concentrations approximately 1 hour after dosing of 6.9 mcg/mL for amoxicillin and 1.6 mcg/mL for clavulanic acid. The areas under the serum concentration curves obtained during the first 4 hours after dosing were 12.6 mcg*h/mL for amoxicillin and 2.9 mcg*h/mL for clavulanic acid when 5 mL of 250 mg/5 mL suspension of AUGMENTIN or equivalent dose of 10 mL of 125 mg/5 mL suspension of AUGMENTIN were administered to normal adults. One 250-mg chewable tablet of AUGMENTIN or two 125-mg chewable tablets of AUGMENTIN are equivalent to 5 mL of 250 mg/5 mL suspension of AUGMENTIN and provide similar serum concentrations of amoxicillin and clavulanic acid.
Amoxicillin serum concentrations achieved with AUGMENTIN are similar to those produced by the oral administration of equivalent doses of amoxicillin alone. Time above the minimum inhibitory concentration of 1 mcg/mL for amoxicillin has been shown to be similar after corresponding every 12 hour and every 8 hour dosing regimens of AUGMENTIN in adults and children.
Absorption: Dosing in the fasted or fed state has minimal effect on the pharmacokinetics of amoxicillin. While AUGMENTIN can be given without regard to meals, absorption of clavulanate potassium when taken with food is greater relative to the fasted state. In one study, the relative bioavailability of clavulanate was reduced when AUGMENTIN was dosed at 30 and 150 minutes after the start of a high‑fat breakfast.
Distribution: Neither component in AUGMENTIN is highly protein‑bound; clavulanic acid is approximately 25% bound to human serum and amoxicillin approximately 18% bound.
Amoxicillin diffuses readily into most body tissues and fluids with the exception of the brain and spinal fluid.
Two hours after oral administration of a single 35 mg/kg dose of suspension of AUGMENTIN to fasting children, average concentrations of 3 mcg/mL of amoxicillin and 0.5 mcg/mL of clavulanic acid were detected in middle ear effusions.
Metabolism and Excretion: The half‑life of amoxicillin after the oral administration of AUGMENTIN is 1.3 hours and that of clavulanic acid is 1 hour.
Approximately 50% to 70% of the amoxicillin and approximately 25% to 40% of the clavulanic acid are excreted unchanged in urine during the first 6 hours after administration of a single 250‑mg or 500‑mg tablet of AUGMENTIN.[1]
References
Adapted from the FDA Package Insert.