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Pharmacological particulars
Pharmacotherapeutic group: Beta-lactam antibacterials, penicillins
ATCvet code: QJ01CR02
Pharmacodynamic properties
Amoxicillin is a beta-lactam antibiotic and its structure contains the beta-lactam ring and thiazolidine ring common to all penicillins. Amoxicillin shows activity against susceptible Gram-positive bacteria and Gram-negative bacteria.
Beta-lactam antibiotics prevent the bacterial cell wall from forming by interfering with the final stage of peptidoglycan synthesis. They inhibit the activity of transpeptidase enzymes, which catalyse cross-linkage of the glycopeptide polymer units that form the cell wall. They exert a bactericidal action but cause lysis of growing cells only.
Clavulanic acid is one of the naturally occurring metabolites of the streptomycete Streptomyces clavuligerus. It has a structural similarity to the penicillin nucleus, including possession of a beta-lactam ring. Clavulanic acid is a beta-lactamase inhibitor acting initially competitively but ultimately irreversibly. Clavulanic acid will penetrate the bacterial cell wall binding to both extracellular and intracellular beta-lactamases.
Amoxicillin is susceptible to breakdown by β-lactamase and therefore combination with an effective ß-lactamase inhibitor (clavulanic acid) extends the range of bacteria against which it is active to include β-lactamase producing species.
In vitro potentiated amoxicillin is active against a wide range of clinically important aerobic and anaerobic bacteria including:
Gram-positive:
Staphylococci (including β-lactamase producing strains)
Clostridia
Streptococci
Gram-negative:
Escherichia coli (including most β-lactamase producing strains)
Campylobacter spp
Pasteurellae
Proteus spp
Resistance is shown among Enterobacter spp, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. A trend in resistance of E. coli is reported.
Pharmacokinetic properties
Amoxicillin is well-absorbed following oral administration. In dogs the systemic bioavailability is 60-70%. Amoxicillin (pKa 2.8) has a relatively small apparent distribution volume, a low plasma protein binding (34% in dogs) and a short terminal half-life due to active tubular excretion via the kidneys. Following absorption the highest concentrations are found in the kidneys (urine) and the bile and then in liver, lungs, heart and spleen. The distribution of amoxicillin to the cerebrospinal fluid is low unless the meninges are inflamed.
Clavulanic acid (pK1 2.7) is also well-absorbed following oral administration. The penetration to the cerebrospinal fluid is poor. The plasma protein binding is approximately 25% and the elimination half-life is short. Clavulanic acid is heavily eliminated by renal excretion (unchanged in urine).
After oral administration of the recommended dose of 12.5mg combined actives/kg to dogs, the following parameters were observed: Cmax of 6.30 +/-0.45µg/ml, Tmax of 1.98 +/- 0.135h and AUC of 23.38 +/- 1.39 µg/ml.h for amoxicillin and Cmax of 0.87 +/- 0.1µg/ml, Tmax of 1.57 +/- 0.177hrs and AUC of 1.56 +/- 0.24mg/ml.h for clavulanic acid.
After oral administration of the recommended dose of 12.5mg combined actives/kg to cats, the following parameters were observed: Cmax of 7.12 +/-1.460 µg/ml, Tmax of 2.69 +/- 0.561 h and AUC of 33.54 +/- 7.335 µg/ml.h for amoxicillin and Cmax of 1.67 +/- 0.381 µg/ml, Tmax of 1.83 +/- 0.227 h and AUC of 7.03 +/- 1.493 µg/ml.h for clavulanic acid.