Ranclav Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Amoxicillin acts through inhibition of biosynthesis of the bacterial cell wall mucopeptide. It is bactericidal against many gram-positive and gram-negative organisms during the stage of active multiplication. However it is susceptible to degradation by beta-lactamases and therefore its spectrum does not include lactamase producing bacteria.
625-mg FC tab: Clavulanic acid is a beta-lactam structurally related to the penicillins, which possess the ability to inactivate a wide range of beta-lactamase commonly found in bacteria resistant to beta-lactam antibiotics.
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.
1-g FC tab and Susp: Clavulanic acid inhibits a wide range of bacterial beta-lactamases and protects amoxicillin from degradation by beta-lactamase enzymes and effectively extends the antibacterial spectrum of amoxicillin to include many beta-lactamase producing strains of bacteria.
Pharmacokinetics: 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. However, administration at the start of a meal improves the absorption of clavulanate and minimize the potential for gastrointestinal intolerance (1-g FC tab and Susp).
The oral bioavailability of amoxicillin and clavulanate potassium is approximately 90% and 75% (FC tab), 75-90% and 75% (Susp), respectively. Clavulanic acid has about the same plasma elimination half-life (1 hr) as that of amoxicillin (1.3 hrs) (FC tab); plasma elimination half-life (0.8-1 hr) as that of amoxicillin (1 hr) (Susp).
Amoxicillin and clavulanic acid are widely distributed to most tissues and body fluids including peritoneal fluid, blister fluid, urine, pleural fluid, middle ear fluid, intestinal mucosa, bone, gallbladder, lung, female reproductive tissues and bile. Penetration into CSF through non-inflamed meninges and into purulent bronchial secretions is low. Amoxicillin and clavulanic acid readily crosses the placenta and are secreted into breastmilk in low concentrations.
Amoxicillin is bound to serum proteins to an extent of 17-20% (FC tab), 20% (Susp) while clavulanic acid is 20-30% (FC tab), 22-30% (Susp) bound to serum proteins.
FC tab: Approximately 10% of the dose of amoxicillin and less than 50% of dose of clavulanate are metabolised.
Amoxicillin and clavulanic acid combination is eliminated primarily unchanged through the renal route (glomerular filtration and tubular secretion). Approximately 50-78% (625-mg FC tab), 50-70% (1-g FC tab), 60-75% (Susp) of amoxicillin and 25-40% (FC tab), 30-40% (Susp) of clavulanic acid are excreted unchanged in urine within the first 6 hrs after administration.
Microbiology: Antibacterial Spectrum: The following pathogens have been found to be susceptible to amoxicillin & clavulanate potassium combination: 625-mg FC tab: Gram-positive bacteria: Staphylococcus aureus (beta-lactamase and non-beta-lactamase producing), Staph. epidermidis (beta-lactamase and non-beta lactamase producing) Staph. saprophyticus, Strep.pneumoniae, Enterococcus faecalis and Strep. viridans. Among anaerobes it is active against Clostridia, Peptocooccus and Peptostreptococcus.
Gram-negative bacteria: N.gonorrhoea, H.influenzae (beta-lactamase and non-beta lactamase producing), Moraxella catarrhalis (beta-lactamase and non-beta lactamase producing), E.coli, Pr. mirabilis, Klebsiella spp., Salmonella spp., Shigella spp. Among anaerobes it is active against bacteroides including B. fragilis.
Resistance: Gram-negative bacilli that produce type I chromosomally mediated beta-lactamases (e.g. Citrobacter, Enterobacter cloacae, Serratia spp., Ps. aeruginosa) are generally resistance to amoxicillin & clavulanate potassium combination since clavulanate potassium does not inhibit type 1 beta lactamase.
1-g FC tab: Gram-positive: Aerobes: Enterococcus faecalis, Strep. pneumoniae, Strep. pyogenes, Strep. viridans, Staphylococcus aureus*, coagulase negative staphylococci* (including Staph. epidermidis*), Corynebacterium spp., Bacillus anthracis, Listeria monocytogenes.
Anaerobes: Clostridium spp., Peptococcus spp., Peptostreptococcus spp.
Gram-negative: Aerobes: H. influenzae*, E. coli*, Pr. mirabilis*, Klebsiella spp.*, Moraxella catarrhalis* (Branhamella catarrhalis), Salmonella spp*., Bordetella pertussis, Brucella spp., N. gonorrhoeae*, N. meningitidis, Vibrio cholerae, Pasteurella multocida.
Anaerobes: Bacteroides spp.* (including B. fragilis).
(Remarks - *including β-lactamase producing strains resistant to Ampicillin and Amoxicillin.)
Susp: Gram-positive: Aerobes: Enterococcus faecalis*, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, Staphylococcus aureus*, Coagulase­-negative staphylococci* (including Staphylococcus epidermidis*), Corynebacterium spp., Bacillus anthracis*, Listeria monocytogenes.
Anaerobes: Clostridium spp., Peptococcus spp., Peptostreptococcus spp.
Gram-negative: Aerobes: Haemophilus influenzae*, Moraxella catarrhalis* (Branhamella catarrhalis), Escherichia coli*, Proteus mirabilis*, Proteus vulgaris*, Klebsiella spp*., Salmonella spp.*, Shigella spp.*, Bordetella pertussis, Brucella spp., Neisseria gonorrhoeae*, Neisseria meningitidis*, Vibrio cholerae, Pasteurella multocida.
Anaerobes: Bacteroides spp.* (including B. fragilis).
* Some members of these species of bacteria produce beta-lactamase, rendering them insensitive to amoxicillin alone.