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 ß-lactamase and therefore combination with an effective ß-lactamase inhibitor (clavulanic acid) extends the range of bacteria against which it is active to include ß-lactamase producing species.
In vitro potentiated amoxicillin is active against a wide range of clinically important aerobic and anaerobic bacteria including:
Gram-positive: Staphylococcus spp. (including β-lactamase producing strains), Streptococcus spp
Gram-negative: Escherichia coli (including most β-lactamase producing strains), Pasteurella spp, 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
After oral administration in dogs, amoxicillin and clavulanic acid are rapidly absorbed. 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 (pKa 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 mainly eliminated by renal excretion (unchanged in urine).
After single oral administration of 17 mg/kg amoxicillin and 4.3 mg/kg clavulanic acid in dogs:
- The maximal plasma concentration (Cmax) of amoxicillin (8.6 µg/mL) was observed 1.5 hour following administration.
- The maximal plasma concentration (Cmax) of clavulanic acid (4.9 µg/mL) was observed 54 minutes following administration.
After single oral administration of 13 mg/kg amoxicillin and 3.15 mg/kg clavulanic acid in cats:
- The maximal plasma concentration (Cmax) of amoxicillin (9.3 µg/mL) was observed 2 hours following administration.
- The maximal plasma concentration (Cmax) of clavulanic acid (4.1 µg/mL) was observed 50 minutes following administration