ATCvet code: QJ01CR02

Amoxicillin is an aminobenzylpenicillin from the β-lactam penicillin family which prevents the bacterial cell wall formation by interfering with the final step of peptidoglycan synthesis.

Clavulanic acid is an irreversible inhibitor of intracellular and extracellular β-lactamases which protects amoxicillin from inactivation by many β-lactamases.

Amoxicillin/clavulanate has a wide range of activity which includes β‑lactamase producing strains of both Gram-positive and Gram-negative aerobes, facultative anaerobes and obligate anaerobes.

Good susceptibility is shown with several gram-positive bacteria including Staphylococci (including beta-lactamase producing strains, MIC90 0.5 μg/ml), Clostridia (MIC90 0.5 μg/ml), Corynebacteria and Streptococci, and gram-negative bacteria including Bacteroides spp (including betalactamase producing strains, MIC90 0.5 μg/ml), Pasteurellae (MIC90 0.25 μg/ml), Escherichia coli (including beta-lactamase producing strains, MIC90 8 μg/ml) and Proteus spp (MIC90 0.5 μg/ml). Variable susceptibility is found in some E. coli.

Susceptibility tests on bacterial pathogens from canine and feline origin revealed the following MIC50 values for a fixed combination of amoxicillin and clavulanic acid (2:1): Proteus spp 0.5 µg/ml and Staphylococcus intermedius 0.094 µg/ml.

Bacteria with a MIC90 of < 2 µg/ml are considered being susceptible and those with a MIC90 of > 8 µg/ml being resistant. Resistance is shown among methicillin-resistant Staphylococcus aureus. A trend in resistance of E. coli is reported.

The pharmacokinetic behaviour of clavulanic acid is roughly comparable with that of amoxicillin. Amoxicillin is well absorbed after oral administration. In dogs, the systemic bioavailability is 60-70%. Amoxicillin (pKa 2.8) has a relatively small apparent distribution volume, low plasma-protein binding (34% in dogs) and a short elimination half-life period due to active tubular excretion by the kidneys. After absorption, highest concentrations are found in the kidneys (urine) and bile, followed by the liver, lungs, heart and spleen.

Distribution of amoxicillin into cerebrospinal fluid is low unless the meninges are inflamed.

Clavulanic acid (pKa 2.7) is also well absorbed after oral administration. Penetration into cerebrospinal fluid is poor. Plasma-protein binding is about 25% and the elimination half-life value is short. Clavulanic acid is largely eliminated by renal excretion (unchanged in the urine).

The pharmacokinetic parameters of the veterinary medicinal product in dogs and cats after oral administration of a dose of 25 mg active material (= 20 mg amoxicillin + 5 mg clavulanic acid) per kg body weight are summarized in the following table: