Pharmaniaga Co-Amoxiclav Mechanism of Action

Pharmacology: Amoxicillin/clavulanate is an antibiotic agent with a broad spectrum of activity against the commonly occurring bacterial pathogens. The amoxicillin is bactericidal in action which inhibits bacterial cell wall synthesis. It inactivates and binds to penicillin-binding proteins located on the inner membrane of the bacterial cell wall, resulting in the weakening of the cell wall and lysis. The β-lactamase inhibitory action of clavulanate extends the spectrum of amoxicillin to embrace a wider range of organisms eg, many resistant to other β-lactam antibiotics.
Resistance to many antibiotics is caused by bacterial enzymes which destroy the antibiotic before it can act on the pathogen. The clavulanate anticipates this defense mechanism by blocking the β-lactamase enzymes; thus, rendering the organisms sensitive to amoxicillin's rapid bactericidal effect at concentrations readily attainable in the body. Clavulanate by itself has little antibacterial activity, however, in association with amoxicillin it produces an antibiotic agent of broad spectrum.
Microbiology: Amoxicillin/clavulanate is bactericidal to a wide range of organisms.
Gram-Positive: Aerobes: Staphylococcus aureus, coagulase-negative staphylococci (including Staphylococcus epidermidis), Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus viridans, Enterococcus faecalis, Bacillus anthracis, Listeria monocytogenes; Corynebacterium sp.
Anaerobes: Clostridium and Peptococcus spp, Peptostretococcus sp.
Gram-Negative: Aerobes: Escherichia coli*, Proteus mirabilis*, Proteus vulgaris*, Klebsiella*, Salmonella* and Shigella spp*, Bordetella pertussis, Brucella sp*, Neisseria meningitidis, Neisseria gonorrhoea*, Haemophilus influenzae*, Pasteurella multocida, Vibrio cholerae, Moraxella catarrhalis.
Anaerobes: Bacteriodes sp eg, Bacteroides fragilis*.
*β-lactamase-producing strains resistant to ampicillin and amoxicillin are included.
Pharmacokinetics: Amoxicillin and potassium clavulanate are well absorbed from the gastrointestinal tract after oral administration. Dosing in the fasted or fed state has minimal effect on the pharmacokinetics of amoxicillin. The pharmacokinetics of the 2 components are closely matched. Peak serum levels both occur about 1 hr after oral administration. Absorption is optimized at the start of a meal. The half-life of amoxicillin after oral administration of the product is 1.3 hrs and that of clavulanic acid is 1 hr. Doubling the dosage of amoxicillin/clavulanate approximately doubles the serum levels achieved.
Approximately 50-70% of the amoxicillin and approximately 25-40% of the clavulanic acid are excreted unchanged in urine during the first 6 hrs after administration of a single amoxicillin/clavulanate 250 or 500 mg tablet.
Concurrent administration of probenecid delays amoxicillin excretion but does not delay renal excretion of clavulanic acid. Neither component is highly protein bound; clavulanic acid has been found to be 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. The results of experiments involving the administration of clavulanic acid to animals suggest that this compound, like amoxicillin, is well distributed in body tissues.