Sullivan Mechanism of Action

Pharmacology: Mechanism of Action: Amoxicillin acts through inhibition of biosynthesis of the bacterial cell wall mucopeptide. It is a bactericidal against susceptible organisms during the stage of active multiplication. Amoxicillin is active against many Gram-positive and Gram-negative pathogens. However, it is susceptible to degradation by beta-lactamase and therefore its spectrum does not include organisms which produce these enzymes. Clavulanic acid is a beta-lactam structurally related to the penicillins, found in microorganisms resistant to penicillins.
The formulation of amoxicillin with clavulanic acid protects amoxicillin from degradation by beta-lactamase enzymes and effectively extends the antibiotic spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other beta-lactam antibiotics.
Pharmacodynamics: Tab 1 g: Amoxicillin is an orally active member of the penicillin family. In amoxicillin, the benzyl ring in site change extends the range of antimicrobial activity, the gram-negative bacteria. It is bactericidal for both gram-positive and negative bacteria.
Clavulanate is a β-lactam antibiotic and interacts with β-lactamase, this interaction may lead to enzyme induction, inactivation of the enzyme and bacteriolysis of the β-lactam ring is used clinically only in combination with amoxicillin. Amoxicillin kills bacteria by interfering with the synthesis of the bacterial cell wall. As the lactamase enzyme secreted by the bacteria destroys amoxicillin, the drug is ineffective in the most staphylococcal infections. Increasing percentage of Salmonella spp., E. coli, Proteus mirabilis, Shigella spp. are not sensitive to amoxicillin. The spectrum of activity of Amoxicillin may be extended by the concomitant use of β-lactamase inhibitors such as clavulanic acid. Clavulanic acid has been reported to enhance activity of amoxicillin, against several species not generally considered sensitive. Clavulanate by itself has little antibacterial activity. However, in association with amoxicillin, it produces an antibiotic agent of broad-spectrum.
Pharmacokinetics: Tab 625 mg/Powd for oral susp 125 mg/31.25 mg/Powd for oral susp 250 mg/62.5 mg/Powd for oral susp 400 mg/57 mg: Amoxicillin and clavulanate potassium are both well absorbed after oral administration and are stable in the presence of gastric acid. Food does not affect the absorption and this combination product may be given without regard to meals. The oral bioavailability of amoxicillin and clavulanic acid are approximately 90% and 75% respectively.
Clavulanic acid has about the same plasma elimination half-life (1 hr) as that of amoxicillin (1.5 hrs).
Amoxicillin and clavulanic acid are widely distributed to most tissues and body fluids including peritoneal fluid, blister fluid, pleural fluid, middle ear fluid, intestinal mucosa, bone, gallbladder, lungs, female reproductive tissues and bile. The secretions is low. Amoxicillin and clavulanic acid readily cross the placenta and are distributed into breast milk into low concentrations. Amoxicillin is bound to serum proteins to an extent of 17-20% while clavulanic acid is 20-30% bound to serum proteins.
Approximately 10% of the dose of amoxicillin and less than 50% of the dose of clavulanic acid are metabolized. Amoxicillin and clavulanic acid are eliminated primarily unchanged through the renal route (glomerular filtration and tubular secretion). Approximately 50-70% of amoxicillin and 25-40% of clavulanic acid are excreted unchanged in urine within the first 6 hours after administration.
Tab 1 g: Amoxicillin and clavulanate potassium are both well absorbed after oral administration and are stable in the presence of gastric acid. Food does not affect the absorption and this combination product may be given without regard to meals. The oral bioavailability of amoxicillin and clavulanic acid is approximately 90% and 75% respectively.
Clavulanic acid has about the same plasma elimination half-life (1 hour) as that of amoxicillin (1.3 hours).
Amoxicillin and clavulanic acid are both widely distributed to most tissues and body fluids including peritoneal fluid, blister fluid, pleural fluid, middle fluid, intestinal mucosa, bone, gallbladder, lungs, female reproductive tissues, and the bile. The penetration into CSF through non-inflamed meninges and into purulent bronchial secretions is low. Amoxicillin and clavulanic acid readily cross the placenta and are distributed into breast milk in low concentrations. Amoxicillin is bound to serum proteins to an extent of 17-20% while clavulanic acid is 20-30% bound to serum proteins.
Approximately 10% of the dose of amoxicillin and less than 50% of dose of clavulanic acid are metabolized.
Amoxicillin and clavulanic acid are eliminated primarily unchanged through the renal route (glomerular filtration and tubular secretion).
Approximately 50-78% of amoxicillin and 25-40% of clavulanic acid are excreted unchanged in urine within the first 6 hours after administration.