MACROLIDES-KSU.pptVIP

MACROLIDES Erythromycin Clarithromycin Azithromycin Mechanism of action Inhibit protein synthesis by binding to the 50 s subunit Antibacterial activity Bactericidal or bacteriostatic, depending on the concentration and type of bacteria Macrolides ( cont. ) Pharmacokinetics Erythromycin base Absorption incomplete but adequate from intestine Inactivated by gastric HCL, hence given as : Enteric coated tablets or ester (stearate, ethyl succinate ) Food delays absorption Not metabolized and actively secreted in bile ( major route of excretion ) Only 2-5 % is excreted in active form in urine Widely distributed into most tissues, except the brain and CSF Cross the placental barrier Protein binding – 70- 80 % Half – life approx. 1.6 hr Clarithromycin Pharmacokinetics Acid stable Food delays absorption but does’nt alter its extent Metabolized by the liver to 14- hydroxy clarithro. ( active ) Widely distributed, except brain and CSF Protein binding 40 – 70 % Excreted in Urine – unchanged 20 – 40 % 14- H. clarithromycin 10 – 15 % Biliary Half- life clarithromycin 3 – 7 hr 14 – H. clarithromycin 5- 9 hr Advantage over erythromycin Lower frequency of GI intolerance Less frequent dosing ( twice daily ) MACROLIDES ( cont. ) Azithromycin Pharmacokinetics Rapidly absorbed from GIT Food delays absorption Widely distributed ( extensive tissue distribution ), except CSF Protein binding 51% Undergo some hepatic metabolism ( inactive ) Biliary route is the major route of elimination Only 6% is excreted unchanged in the urine Half- life approx. 3 days Advantage over erythromycin clarithromycin Once daily dosing No inhibition of cytochrome P- 450 Macrolides ( cont. ) Antibacterial spectrum Erythromycin – Mainly effective on G+ bacteria A. Gram- positive bacteria Staph. Aureus S. pneumoniae URTIs ( eg. Otitis media, pharyngitis ) L