AMK Mechanism of Action

Tablet: Pharmacology: AMK is a combination of amoxicillin and clavulanic acid. Amoxicillin, a penicillin antibiotic with a broad spectrum of bactericidal activity, and clavulanic acid, an irreversible beta-lactamase inhibitor. With enzymes it produces stable nonactive complexes and protects amoxicillin from degradation.
Antibacterial Spectrum: Gram-positive aerobes (S. pneumonia, S. pyogenes, S. viridans, S. aureus); Gram-negative aerobes (H. influenzae, Moraxella catarrhalis, E. coli, Klebsiella spp., N. gonorrhoeae); Anaerobes (Peptostreptococcus spp.).
Pharmacokinetics: Amoxicillin and Clavulanic acid are both well absorbed after oral administration and are stable in the presence of gastric acid. Food has no effect on the degree of absorption.
Peak serum concentrations are achieved approximately 1-2.5 hours after ingestion. Amoxicillin and Clavulanate potassium combination is eliminated primarily unchanged through the renal route. In patients with impaired renal function excretion of the drug from the body is delayed.
Powder for oral suspension: Pharmacology: Pharmacokinetics: Absorption: Amoxicillin trihydrate and clavulanate potassium are both generally stable in the presence of acidic gastric secretions and are well absorbed following oral administration of amoxicillin and clavulanate potassium. Peak serum concentrations of amoxicillin and of clavulanic acid are generally attained within 1-2.5 hours following oral administration of a single dose of conventional preparations of amoxicillin and clavulanate potassium in fasting adults.
Distribution: Following administration of amoxicillin and clavulanate potassium, amoxicillin and clavulanic acid are both distributed into the lungs, pleural fluid, and peritoneal fluid. Low concentrations of each drug are attained in sputum and saliva. Only minimal concentrations of amoxicillin or clavulanic acid are attained in CSF following oral administration of amoxicillin and clavulanate potassium in patients with uninflamed meninges; higher concentrations may be attained when meninges are inflamed. Amoxicillin is 17-20% bound to serum proteins. In vitro or in vivo following oral administration, clavulanic acid is reportedly 22-30% bound to serum proteins at concentration of 1-100 μg/ml.
Amoxicillin and clavulanic acid readily cross the placenta. Amoxicillin and clavulanic acid are distributed into milk in low concentrations.
Elimination: Following oral administration of a single oral dose of amoxicillin and clavulanate potassium in adults with normal renal function, amoxicillin has an elimination half-life of 1-1.3 hours and clavulanic acid has a distribution half-life of 0.28 hours and an elimination half-life of 0.78-1.2 hours.
The metabolic fate of clavulanate potassium has not been fully elucidated; however, the drug appears to be extensively metabolized. In rats and dogs, the major metabolite of clavulanic acid is 1-amino-4-hydroxybutan-2-one; this metabolite has also been found in human urine following administration of clavulanic acid. Clavulanic acid is excreted in urine principally by glomerular filtration.
Following oral administration of a single oral dose of amoxicillin and clavulanate potassium in adults with normal renal function, approximately 50-73 and 25-45% of the amoxicillin and clavulanic acid doses, respectively, are unchanged in urine within 6-8 hours.
Serum concentrations of amoxicillin and of clavulanic acid are higher and the serum half-lives prolonged in patients with renal impairment.
Pharmacodynamics: Amoxicillin and clavulanate potassium usually is bactericidal in action. Concurrent administration of clavulanic acid does not alter the mechanism of action of amoxicillin. However, because clavulanic acid has a high affinity for and binds to certain β-lactamase that generally inactivates amoxicillin by hydrolyzing its β-lactam ring, concurrent administration of the drug with amoxicillin results in synergistic bactericidal effect which expands the spectrum of activity of amoxicillin against many strains of β-lactamase-producing bacteria that are resistant to amoxicillin alone.
Clavulanic acid generally acts as an irreversible, competitive inhibitor of β-lactamase. The mechanism by which clavulanic acid binds to and inhibits β-lactamase varies depending on the specific β-lactamase involved. Because clavulanic acid is structurally similar to penicillins and cephalosporins, it initially acts as a competitive inhibitor and binds to the active site on the β-lactamase.