Amoxicillin
Amoxil®, DisperMox®, Wymox®, Trimox® | Amoxicot™ | Moxilin™ | Sumox™
Classification:
Antiinfective Agents
Description: Amoxicillin is an oral semisynthetic aminopenicillin similar to ampicillin. The aminopenicillins are not stable to beta-lactamases of either gram-positive or gram-negative bacteria. Amoxicillin is more stable to gastric acid than is penicillin and more bioavailable than oral ampicillin. Because of greater bioavailability, amoxicillin is associated with a lower incidence of diarrhea versus orally-administered ampicillin. Like ampicillin, amoxicillin has a broader spectrum of activity than penicillin, although the carboxy- and ureidopenicillins are much more active against gram-negative rods. Amoxicillin is commonly used to treat infections such as otitis media, bronchitis, sinusitis, and bacterial cystitis caused by susceptible organisms. To increase the efficacy of amoxicillin against penicillin-resistant S. pneumoniae in otitis or respiratory infections, higher dosage regimens have been recommended. Amoxicillin is routinely used for endocarditis prophylaxis. Amoxicillin is also used in various regimens for the treatment of Helicobacter pylori infection. Due to the increasing prevalence of resistant strains of N. gonorrhoeae, aminopenicillins are no longer recommended for the treatment of gonorrhea. Amoxicillin was approved by the FDA in 1974. A new dosage form of amoxicillin, DisperMox™ (amoxicillin tablets for oral suspension), was approved August 11, 2003.
Mechanism of Action: Beta-lactam antibiotics such as amoxicillin are mainly bactericidal. Like other penicillins, amoxicillin inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. Penicillin-binding proteins are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. Penicillin-binding proteins vary among different bacterial species. Thus, the intrinisic activity of amoxicillin, as well as the other penicillins, against a particular organism depends on their ability to gain access to and bind with the necessary PBP. The aminopenicillins are able to penetrate gram-negative bacteria more readily than are the natural penicillins or penicillinase-resistant penicillins due to the presence of a free amino group within the structure. Like all beta-lactam antibiotics, amoxicillin’s ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor.
Amoxicillin’s gram-positive spectrum is similar to the natural penicillins, although amoxicillin is slightly less active than penicillin G against S. pyogenes, S. pneumoniae, S. and agalactiae and slightly more active against enterococci. Like penicillin G and penicillin V, amoxicillin is susceptible to beta-lactamases from staphylococci. Because the majority of Staphylococci produce beta-lactamases, amoxicillin is not routinely used to treat staphylococcal infections. Amoxicillin is effective against most streptococci. Penicillin-resistant strains of S. pneumoniae are increasing in number. The mechanism of resistance is mediated via the development of altered PBPs and the penicillin-resistant strains will generally be resistant to amoxicillin. The addition of clavulanic acid does not overcome this type of resistance. Increased dosages of amoxicillin may be necessary to overcome resistant S. pneumoniae. Community resistance patterns may determine the likelyhood of amoxicillin efficacy against S. pneumoniae. Most oral, gram-positive anaerobes are sensitive. Gram-negative bacteria that are frequently susceptible include N. meningitidis, H. influenzae, Gardnerella vaginalis, Bordetella pertussis, and some enteric bacilli including E. coli, Proteus mirabilis, and Salmonella. An increasing number of strains of N. gonorrhoeae are resistant to amoxicillin. In addition, because of increasing bacterial resistance, amoxicillin’s activity against some strains of E. coli, Salmonella, and Shigella has been declining. Although amoxicillin frequently is used to treat H. influenzae, a significant percentage of this organism is beta-lactamase-producing, rendering the drug ineffective. Most Klebsiella, Serratia, Acinetobacter, indole-positive Proteus, Pseudomonas, and Bacteroides fragilis are resistant. Amoxicillin has activity against Helicobacter pylori, but must be combined with other agents to improve erradication rates. Clinicians are advised to consult susceptibility data at the institution in which they practice to determine a given organism’s susceptibility.
Pharmacokinetics: Amoxicillin is administered orally. It is stable against gastric acid and is rapidly absorbed from the GI tract. Oral bioavailability ranges from 74 - 92%. Amoxicillin is more completely absorbed than ampicillin and, for this reason, is often the preferred oral aminopenicillin. Peak serum levels of amoxicillin occur within 1 - 2.5 hours following an oral dose. Food in the stomach inhibits the rate of absorption but not its extent; amoxicillin may be given without regard to meals. Approximately 17 - 20% of the circulating drug is protein-bound. Amoxicillin is distributed into liver; lungs; gallbladder; prostate; urine; middle ear effusions; bronchial secretions; maxillary sinus secretions; and peritoneal, pleural, and synovial fluids. Minimal levels within the CSF are attained when meninges are not inflamed; these levels are increased with inflammation. Amoxicillin does cross the placenta. A small percentage is excreted in breast milk.
Amoxil Capsules(Cap 250 mg )
Only 10% of an amoxicillin dose is hepatically metabolized to inactive derivatives. The unchanged drug and its metabolites are excreted into the urine primarily via tubular secretion and glomerular filtration. Approximately 60% of an orally administered dose is excreted in the urine within 6 - 8 hours. In patients with normal renal function, the elimination half-life of amoxicillin is 1 - 1.5 hours. The elimination half-life increases as renal function declines. It may be as long as 7.5 hours in patients with end-stage renal disease. Dosages need to be adjusted accordingly.
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References
. Howden CW, Hunt RH. Guidelines for the management of Helicobacter pylori infection. Am J Gastroenterol 1998;93:2330 - 8.
[ Revised 3/1/2006 9:36:00 AM ]
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