Klaryth Mechanism of Action

Pharmacology: Pharmacodynamics: Clarithromycin is more active against susceptible streptococci and staphylococci in vitro. The minimum inhibitory concentrations of Clarithromycin are usually two- to fourfold lower than for erythromycin.
Clarithromycin is more active against some mycobacteria and have some in vitro activity against the protozoan Toxoplasma gondii, and may have some activity against cryptosporidium.
The major metabolite, 14-hydroxylclarithromycin, is also active, and may enhance the activity of Clarithromycin in vivo, notably against Haemophilus influenzae.
Clarithromycin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections: Gram-positive Aerobes microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Listeria monocytogenes.
Gram-negative Aerobes microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhea, Legionella pneumophila.
Other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae (TWAR strain), Ureaplasma urealyticum.
Mycobacteria: Mycobacteria kansasii, Mycobacterium leprae and Mycobacterium avium complex (MAC) which includes: Mycobacterium avium, Mycobacterium intracellulare.
*Most strains of methicillin-resistant and oxacillin-resistant staphylococci are resistant to Clarithromycin.
Clarithromycin exhibits in vitro activity against most strains of the following microorganisms, but their clinical significance is unknown.
Gram-positive Aerobes microorganisms: Streptococcus agalactiae, Streptococci (Group C, F, G), Viridans group streptococci.
Gram-negative Aerobes microorganisms: Bordetella pertussis, Pasteurella multocida.
Gram-positive Anaerobes microorganisms: Bacteroides melaninogenicus.
Spirochetes: Borrelia burgdorferi, Treponema pallidum.
Campylobacter: Campylobacter jejuni.
Pharmacokinetics: Clarithromycin is rapidly absorbed from the gastrointestinal tract following oral administration, and undergoes first-pass metabolism; the bioavailability of the parent drug is about 55%. The extent of absorption is relatively unaffected by the presence of food. Peak concentrations of Clarithromycin and its principal active metabolite 14-hydroxylclarithromycin are reported to be about 0.6 and 0.7 μg per mL respectively following a single 250 mg dose by mouth; at steady-state the same dose given every 12 hours as tablets produce peak concentrations of Clarithromycin of about 1 μg per mL. The same dose given as a suspension produces a steady-state plasma concentration of about 2 μg per mL.
The pharmacokinetics of Clarithromycin are non-linear and dose dependent; high doses may produce disproportionate increases in peak concentration of the parent drug, due to saturation of the metabolic pathways.
The drug and its principal metabolite are widely distributed, and tissue concentrations exceed those in serum, in part because of intracellular uptake. Clarithromycin has been detected in breast milk. It is extensively metabolized in the liver, and excreted in feces via the bile. Substantial amounts are excreted in urine; at steady-state about 20% and 30% of a 250 mg or 500 mg dose, respectively, is excreted in this way, as unchanged drug. 14-Hydroxylclarithromycin as well as other metabolites are also excreted in the urine accounting for 10 to 15% dose. The terminal half-life of Clarithromycin is reportedly about 3 to 4 hours in patients receiving 250 mg doses twice daily, and about 5 to 7 hours in those receiving 500 mg twice daily. The half-life is prolonged in renal impairment.