Amoxicillin exerts its bactericidal activity by interfering with the bacterial cell wall synthesis. Peptidoglycan is a heteropolymeric structure that provides the cell wall with mechanical stability. The final stage of peptidoglycan synthesis involves the completion of the cross-linking when the terminal glycine residue of the pentaglycine bridge is linked to the fourth residue of the pentapeptide. The transpeptidase that catalyzes this step is inhibited by penicillins. As a result, the bacterial cell wall is weakened, the cell swells, and then ruptures. Amoxicillin is readily hydrolyzed by the staphylococcal penicillinase.
After oral administration, amoxicillin is stable in gastric acid and about 74-92% of a single oral dose of the drug is absorbed from the gastrointestinal (GI) tract of fasting adults. Peak serum concentrations (Cmax
) of amoxicillin are generally attained within 1-2 hours and serum concentrations are usually low and undetectable 6-8 hours later. Increasing the dose results in a corresponding increase in Cmax
and area under the serum concentration-time curves (AUC).
After oral administration of a single dose of amoxicillin 250 or 500 mg, the Cmax
were 3.5-5 or 5.5-11 mcg/mL, respectively. In a study in healthy, fasting adults who received a single oral dose of amoxicillin 500 mg, the mean serum drug concentrations were 3.3, 6.7, 9.3, 5.8, and 0.6 mcg/mL at 30 minutes, 1 hour, 2 hours, 3 hours, and 4 hours, respectively, after the dose.
In children 4 to 45 months old given amoxicillin oral suspension 15 mg/kg daily, the serum drug concentrations ranged from 2.4-8.5, 1.9-11.3, 1.7-6.4, 0.17-1.9, and 0.14-3.3 mcg/mL at 30 minutes, 1 hour, 2 hours, 4 hours, and 6 hours, respectively, after a dose.
Oral absorption of amoxicillin is delayed in neonates compared with absorption in children and adults. After oral administration of a single dose of amoxicillin in neonates, the Cmax
is generally attained within 3-4.5 hours compared with 1-2 hours in children and adults.
The apparent volume of distribution of amoxicillin ranges from 0.267 to 0.315 L/kg in adults with normal renal function. Amoxicillin is generally distributed into ascitic, synovial, and pleural fluids, middle ear effusions, bronchial and maxillary sinus secretions, sputum, and tonsils. It is also distributed into the liver, lungs, gallbladder, prostate, and muscle. Low concentrations of the drug are also attained in saliva, sweat and tears. Amoxicillin is distributed into bile in varying amounts. If biliary obstruction is not present, amoxicillin concentration in bile is generally 1-30 times greater than concurrent serum concentrations of the drug. As with other penicillins, only negligible amounts of amoxicillin have been detected in aqueous humor. Minimal drug concentrations are attained in cerebrospinal fluid (CSF) of patients with uninflamed meninges; higher concentrations may be attained when meninges are inflamed.
Amoxicillin readily crosses the placenta and is distributed into human milk in low concentrations. Amoxicillin concentrations in cord blood are reportedly 25-33% of concurrent maternal serum concentrations. About 17-20% of the drug is bound to serum proteins.
As with other penicillins, amoxicillin is excreted by renal tubular secretion and to a lesser extent by glomerular filtration. Small amounts of the drug are also excreted in feces and bile. About 19-33% of the drug is excreted in urine as penicilloic acid, which is a microbiologically inactive metabolite.
Serum concentration of amoxicillin is generally higher and serum half-life (t1/2
) is longer in neonates than in older children or adults. In general, the serum t1/2
of the drug is inversely proportional to birthweight, gestational age and chronologic age. This appears to result from immature mechanisms for renal tubular secretion of the drug. The serum t1/2
of amoxicillin is about 3.7 hours in full-term neonates, and 0.9-1.9 hours in infants and children.
Amoxicillin is removed by hemodialysis. Only minimal amounts appear to be removed by peritoneal dialysis.
Microbiology: Antimicrobial Spectrum of Activity:
Amoxicillin is a broad spectrum aminopenicillin antibiotic that is structurally related to ampicillin. It is rapidly bactericidal against susceptible organisms during the stage of active multiplication. Amoxicillin is ineffective in most staphylococcal infections since it is destroyed by β-lactamase.
Amoxicillin is active in vitro
and in clinical infections against most strains of the following microorganisms: See Table 1.
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Staphylococci which are susceptible to amoxicillin but resistant to methicillin/oxacillin should be considered as resistant to amoxicillin.
The following microorganisms are generally sensitive to amoxicillin in vitro
: See Table 2.
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It is suggested to carry out susceptibility tests.