Coklav Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: 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-lactamases that generally inactivate amoxicillin by hydrolyzing its β-lactam ring, concurrent administration of the drug with amoxicillin results in a synergistic bactericidal effect which expands the spectrum of activity of amoxicillin against many strains of β-lactamases-producing bacteria that are resistant to amoxicillin alone.
Clavulanic acid generally acts as an irreversible, competitive inhibitor of β-lactamases. The mechanism by which clavulanic acid binds to and inhibits β-lactamases 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-lactamases. An inactive acyl intermediate is then formed but it is only transiently inactive since the intermediate can be hydrolyzed, resulting in restoration of β-lactamases activity and release of clavulanic acid degradation products. With many types of β-lactamases, however, subsequent reactions occur that lead to irreversible inactivation of the β-lactamases.
Pharmacokinetics: 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 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. Following administration of amoxicillin and clavulanate potassium, amoxicillin and clavulanic acid are both distributed into the lungs, pleural fluid, and peritoneal fluid. Low concentrations (i.e., less than 1 mcg/ml) of each drug are attained in sputum and saliva. Amoxicillin and clavulanic acid readily cross the placenta. Amoxicillin and clavulanic acid are distributed into milk in low concentrations. Amoxicillin has an elimination half-life of 1-1.3 hours and clavulanic acid has an elimination half-life of 0.78-1.2 hours. Approximately 50 to 73% of the amoxicillin and approximately 25 to 45% of the clavulanic acid are excreted unchanged in the urine within the 6-8 hours after administration.