Clarithromycin Stella Mechanism of Action

Pharmacology: Pharmacodynamics: Clarithromycin exerts its antibacterial action by binding to the 50S ribosomal subunit of susceptible microorganisms resulting in inhibition of protein synthesis.
Clarithromycin is active in vitro against a variety of aerobic and anaerobic gram-positive and gram-negative microorganisms as well as most Mycobacterium avium complex (MAC) microorganisms.
Additionally, the 14-hydroxyclarithromycin metabolite also has clinically significant antimicrobial activity. The14-hydroxyclarithromycin is twice as active against Haemophilus influenzae microorganisms as the parent compound. However, for Mycobacterium avium complex (MAC) isolates the 14-hydroxymetabolite is 4 to 7 times less active than clarithromycin. The clinical significance of this activity against Mycobacterium avium complex is unknown.
Pharmacokinetics: Clarithromycin is rapidly absorbed from the gastrointestinal tract, 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-hydroxyclarithromycin, are reported to be about 900 and 600 ng/ml, respectively after a single 250 mg dose by mouth; at steady state the same dose given every 12 hours as tablets produces peak concentrations of clarithromycin of about 1 mg/ml.
The pharmacokinetics of clarithromycin are non-linear and dose dependent; high doses may produce disproportionate increases in peak concentrations of the parent drug, due to saturation of the metabolic pathways.
Clarithromycin 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 metabolised in the liver, and excreted in faeces via the bile. At steady state about 20% and 30% of a 250 mg or 500 mg dose as tablets, respectively, is excreted in the urine as unchanged drug. 14-hydroxyclarithromycin as well as other metabolites are also excreted in the urine accounting for 10 to 15% of the 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.