Augmentin/Augmentin ES Mechanism of Action

Pharmacotherapeutic group: Combinations of penicillins, incl. beta-lactamase inhibitors. Anatomical Therapeutic Chemical (ATC) code: J01CR02.
PHARMACOLOGY: Pharmacodynamics: Augmentin tablet: Resistance to many antibiotics is caused by bacterial enzymes which destroy the antibiotic before it can act on the pathogen. The clavulanate in Augmentin anticipates this defence mechanism by blocking the beta-lactamase enzymes, thus rendering the high concentration of Amoxicillin effected on bactericidal in the body.
Clavulanate by itself has little antibacterial activity; however, in association with amoxicillin as Augmentin, it can be antibiotic agent of bacterial resistant Amoxicillin by producing β-lactamase for destroying. It can be treated the bacterial infection in with wide application in hospital and general practice.
Augmentin suspension 228 mg/5 mL and 457 mg/5 mL: Resistance to many antibiotics is caused by bacterial enzymes which destroy the antibiotic before it can act on the pathogen. The clavulanate in Augmentin suspension anticipates this defence mechanism by blocking the beta-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 as Augmentin, it produces an antibiotic agent of broad spectrum with wide application in hospital and general practice.
Mechanism of Action: Augmentin ES suspension: Amoxicillin is a semisynthetic antibiotic with a broad spectrum antibacterial activity against many gram-positive and gram-negative microorganisms. Amoxicillin is, however, susceptible to degradation by beta-lactamases, and therefore the spectrum of activity of amoxicillin alone does not include organisms which produce these enzymes.
Clavulanate is a beta-lactam, structurally related to the penicillins, which possesses the ability to inactivate a wide range of beta-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid mediated beta-lactamases frequently responsible for transferred drug resistance. It is generally less effective against chromosomally-mediated type 1 beta-lactamases.
The clavulanate component in Augmentin ES protects amoxicillin from degradation by beta-lactamase enzymes, and effectively extends the antibacterial spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other penicillins and cephalosporins. Thus, Augmentin ES possesses the distinctive properties of a broad-spectrum antibiotic and a beta-lactamase inhibitor.
Pharmacodynamic Effects: In the list as follows, organisms are categorised according to their in vitro susceptibility to Augmentin. (See Table 1.)

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Augmentin suspension 228 mg/5 mL and 457 mg/5 mL: Infections caused by amoxicillin-susceptible organisms are amenable to Augmentin treatment due to its amoxicillin content. Mixed infections caused by amoxicillin-susceptible organisms in conjunction with Augmentin-susceptible beta-lactamase producing organisms are therefore considered to be treated with Augmentin.
Pharmacokinetics: Augmentin tablet: The pharmacokinetics of the two components of Augmentin, amoxicillin and clavulanate are similar and both can well absorb in the digestive tract. Peak serum levels of both occur about 1 hour after oral administration. Absorption of Augmentin is optimised at the start of a meal. Augmentin has a mean elimination half-life of approximately one hour.
Doubling the dosage of Augmentin approximately doubles the serum levels achieved.
Both clavulanate and amoxicillin have low levels of serum binding; about 70% remains free in the serum.
Augmentin suspension 228 mg/5 mL and 457 mg/5 mL: Absorption: The two components of Augmentin suspension 228 mg/5 mL and 457 mg/5 mL, amoxicillin and clavulanate, are each fully dissociated in aqueous solution at physiological pH. Both components are rapidly and well absorbed by the oral route of administration. Absorption of Augmentin is optimised when taken at the start of a meal.
The mean AUC values for amoxicillin are essentially the same following twice a day dosing with the Augmentin 1g tablets (875/125 mg) or three times a day dosing with the Augmentin 625 mg tablets (500/125 mg), in adults. No differences between the 875 mg twice daily and 500 mg three times daily dosing regimens are seen when comparing the amoxicillin T_½, or C_max after normalisation for the different doses of amoxicillin administered. Similarly, no differences are seen for the clavulanate T_½, C_max or AUC values after appropriate dose normalisation.
The time of dosing of Augmentin relative to the start of a meal has no marked effects on the pharmacokinetics of amoxicillin in adults. In a study of the Augmentin 1g tablets (875/125 mg), the time of dosing relative to ingestion of a meal had a marked effect on the pharmacokinetics of clavulanate. For clavulanate AUC and C_max, the highest mean values and smallest inter-subject variabilities were achieved by administering Augmentin at the start of a meal, compared to the fasting state or 30 or 150 minutes after the start of a meal.
The mean C_max, T_max, T_½ and AUC values for amoxicillin and clavulanate are given as follows for Augmentin 1g tablets (an 875 mg/125 mg dose of amoxicillin/clavulanate) administered at the start of a meal. (See Table 2.)

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Amoxicillin serum concentrations achieved with Augmentin are similar to those produced by the oral administration of equivalent doses of amoxicillin alone.
Distribution: The pharmacokinetics of the two components of Augmentin are closely matched. Both clavulanate and amoxicillin have low levels of serum binding; about 70% remains free in the serum.
Doubling the dosage of Augmentin approximately doubles the serum levels achieved.
Augmentin ES suspension: Pharmacokinetic parameters are given as follows for Augmentin ES administered at 45 mg/kg every 12 hours to paediatric patients. (See Table 3.)

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The pharmacokinetics of the two components of Augmentin ES are closely matched. Both clavulanate and amoxicillin have low levels of serum binding; about 70% remains free in the serum.
Toxicology: Preclinical safety data: No further information of relevance.