Sign Out
Pharmacology: Pharmacodynamics: Amoxicillin (an aminopenicillin antibiotic) and potassium clavulanate (a β-lactamase inhibitor) (Co-amoxiclav) is usually 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 synergistic bactericidal effect which expands amoxicillin's spectrum of activity against many strains of β-lactamase-producing bacteria resistant to amoxicillin alone.
Pharmacokinetics: Tablet: Co-amoxiclav is stable in the presence of acidic gastric secretions and is well absorbed following oral administration.
In a single-dose study in healthy male and female subjects, 19 to 44 years old, oral administration of Co-amoxiclav 1 g tablet resulted in mean peak serum amoxicillin and clavulanic acid concentrations (Cmax) of 7.787 mcg/mL and 3.078 mcg/mL, respectively. Peak serum concentrations of amoxicillin and of clavulanic acid were generally attained within 1 to 2.5 hours after oral administration. The area under the plasma concentration time curve (AUC0-t) for amoxicillin and clavulanic acid were 30.533 mcg/mL·hr and 7.184 mcg/mL·hr, respectively, while AUC0-∞ were 31.615 mcg/mL·hr and 7.487 mcg/mL·hr, respectively.
When a single oral dose of Co-amoxiclav 625 mg tablet was administered in adult subjects (fasted state), pharmacokinetic parameters reached were: Cmax 7.03 mcg/mL, AUC0-t 19.49 mcg/mL·hr, AUC0-∞ 20.91 mcg/mL·hr, and half-life (t½) 1.04 hours for amoxicillin, and Cmax 2.143 mcg/mL, AUC0-t 4.064 mcg/mL·hr, AUC0-∞ 4.722 mcg/mL·hr and t½ 1.2 hours for clavulanic acid.
Studies in healthy adults using Co-amoxiclav indicate that presence of food in the gastrointestinal tract does not affect oral absorption of either amoxicillin or clavulanic acid.
Therapeutic concentrations of both amoxicillin and clavulanic acid have been found in the gall bladder, abdominal tissue, skin, fat, and muscle tissues; the synovial and peritoneal fluids, bile and pus. Animal studies show no evidence that either component may accumulate in any organ.
Neither amoxicillin nor clavulanic acid is highly protein-bound; studies show that about 13% to 25% of total plasma drug concentration of each compound is protein-bound.
Both Co-amoxiclav components readily cross the placenta. Only small amounts of amoxicillin and clavulanic acid are distributed in human milk.
Serum concentrations of amoxicillin and clavulanic acid both decline in a biphasic manner and their t½ are similar. Approximately 50 to 73% of amoxicillin and 25 to 45% of clavulanic acid are excreted unchanged in urine within 6 to 8 hours following oral administration of a single dose of Co-amoxiclav in adults with normal renal function.
Powder for injection: At physiologic pH, both amoxicillin and clavulanic acid are fully dissociated in aqueous solution.
When Co-amoxiclav 600 mg (500 mg/100 mg) was given as a bolus intravenous (IV) injection in healthy subjects, the mean peak serum amoxicillin and clavulanic concentrations (Cmax) were 32.2 mcg/mL and 10.5 mcg/mL, respectively. The area under the plasma concentration time curve (AUC) for amoxicillin and clavulanic acid were 25.5 hr·mcg/mL and 9.2 hr·mcg/mL, respectively.
When Co-amoxiclav 1.2 g (1000 mg/200 mg) was given as a bolus IV injection in healthy subjects, the mean amoxicillin and clavulanic acid Cmax values were 105.4 mcg/mL and 28.5 mcg/mL, respectively. The AUC for amoxicillin and clavulanic acid were 76.3 hr·mcg/mL and 27.9 hr·mcg/mL, respectively.
After IV administration, therapeutic concentrations of both amoxicillin and clavulanic acid may be detected in the tissues and interstitial fluid. Therapeutic concentrations of both drugs have been found in the gall bladder, abdominal tissue, skin, fat, and muscle tissues; the synovial and peritoneal fluids, bile and pus. Animal studies show no evidence that either component may accumulate in any organ.
Neither amoxicillin nor clavulanic acid is highly protein-bound; about 13% to 25% of total plasma drug concentration of each compound is protein-bound.
Both Co-amoxiclav components readily cross the placenta. Only small amounts of amoxicillin and clavulanic acid are distributed in human milk.
Serum concentrations of amoxicillin and clavulanic acid both decline in a biphasic manner and their half-lives (0.9 to 1.1 hours) are similar.
As with other penicillins, amoxicillin is primarily eliminated via the kidneys, whereas clavulanate undergoes both renal and non-renal excretion. About 60% to 70% of amoxicillin and about 40% to 65% of clavulanic acid are excreted unchanged in urine during the first 6 hours after a single bolus IV administration of Co-amoxiclav 600 mg (500 mg/100 mg) or 1.2 g (1000 mg/200 mg) injection.
Amoxicillin is also partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to 10% to 25% of the initial dose. Clavulanic acid is extensively metabolized in man to 2,5 dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one and eliminated in urine and feces as carbon dioxide in expired air.
Amoxicillin and clavulanic acid are both removed by hemodialysis.
Microbiology: Antimicrobial Spectrum of Activity: In vitro and clinical studies have demonstrated the susceptibility of the following microorganisms to Co-amoxiclav: See Tables 1, 2 and 3.
Click on icon to see table/diagram/image
Click on icon to see table/diagram/image
Click on icon to see table/diagram/image
Continue with Google