Erythromycin protein binding

The macrolides are orally absorbed but they are acid-labile. They therefore need to be administered in acid-resistant capsules or as acid-resistant esters. The macrolides are widely distributed into all fluids except the CNS. Protein binding is about 90%. They are eliminated via biliary excretion with extensive enterohepatic circulation. Elimination half-lives vary from 1.4 h for erythromycin to 40-60 h for azithromycin. 

Protein Binding. In plasma, erythromycin about 70 to 80%, erythromycin propionate about 90 to 99%, erythromycin stearate about 90%. 

Disopyramide altered protein binding of erythromycin and this resulted in increased plasma erythromycin concentrations in vitro (72). The interaction between erythromycin and disopyramide was potentially fatal in two cases (73). 

The macrolides distribute well and tissue concentrations may be higher than serum concentrations. Erythromycin concentrates and is active in leukocytes because of its high lipid solubility and ion trapping. The of erythromycin is 3.7-7.21/kg in adult horses and foals. The protein binding is low. The hepatic clearance of the macrolides may be slower in animals of up to 1 month of age than in adult animals. 

IS% of the 14-hydroxy metabolite is excreted in the urine. Biliary excretion of clarithromycin is much lower than that of erythromycin. Clarithromycin is widely distributed into the tissues, which retain much higher concentrations than the plasma. Protein-binding fractions in the plasma range from 65 to 70%. The plasma half-life of clarithromycin is 4.3 hours. 

Erythromycin (E-Mycin, Erythrocin, Erythrocin Lactobionate) Protein-Binding 65% Half-Life PO 1-2 hours IV 3-5 hours PO 250-500 mg Every 6 hours... 

Erythromycin, dirithromycin (Dynabac) Protein-Binding Unknown Half-Life 20-50 hours Pregnancy Category C PO 250 mg Every 6 hours... 

Carbamazepine is metabolized to an active 10,11-epoxide metabolite, thus medications that inhibit 3A4 isoenzymes may result in carbamazepine toxicity (e.g., cimetidine, dUtiazem, erythromycin, fluoxetine, fluvoxamine, isoniazid, itraconazole, ketoconazole, nefa-zodone, propoxyphene, and verapamil). " When carbamazepine is combined with valproate, the carbamazepine dose should be reduced because valproate displaces carbamazepine from protein binding sites, thus increasing free levels." Combining clozapine and carbamazepine is not recommended because of the possibdity of bone marrow suppression with both agents. ... 

Erythromycin diffuses readily into intracellular fluids, achieving antibacterial activity in essentially all sites except the brain and CSF. Erythromycin penetrates into prostatic fluid, achieving concentrations approximately 40% of those in plasma. Concentrations in middle ear exudate reach only 50% of serum concentrations, and thus may be inadequate for the treatment of otitis media caused by H. influenzae. Protein binding is approximately 70 to 80% for erythromycin base and even higher, 96%, for the estolate. Erythromycin traverses the placenta, and drug concentrations in fetal plasma are about 5 to 20% of those in the maternal circulation. Concentrations in breast milk are 50% of those in serum. 

Ribosomal Protein Synthesis Inhibitors. Figure 5 Nucleotides at the binding sites of chloramphenicol, erythromycin and clindamycin at the peptidyl transferase center. The nucleotides that are within 4.4 A of the antibiotics chloramphenicol, erythromycin and clindamycin in 50S-antibiotic complexes are indicated with the letters C, E, and L, respectively, on the secondary structure of the peptidyl transferase loop region of 23S rRNA (the sequence shown is that of E. coll). The sites of drug resistance in one or more peptidyl transferase antibiotics due to base changes (solid circles) and lack of modification (solid square) are indicated. Nucleotides that display altered chemical reactivity in the presence of one or more peptidyl transferase antibiotics are boxed. 

The macrolide erythromycin inhibits protein synthesis and resistance is induced by N -dimethyl-ation of adenine within the 23S rRNA, which results in reduced affinity of ribosomes for antibiotics related to erythromcin (Skinner et al. 1983). Sulfonamides function by binding tightly to chromosomal dihydropteroate synthetase and resistance to sulfonamides is developed in the resistance plasmid through a form of the enzyme that is resistant to the effect of sulfonamides. 

Macrolides Erythromycin Inhibits protein synthesis by binding Gram-positive cocci, mycoplasma,... 

Newer and more generally usefnl macrolide antibiotics include azithromycin (Zithromax) and clarithromycin (Biaxin). These too are wide-spectrum antibiotics and both are semisynthetic derivatives of erythromycin. Like the tetracyclines, the macrolide antibiotics act as protein synthesis inhibitors and also do so by binding specifically to the bacterial ribosome, thongh at a site distinct from that of the tetracyclines. 

Erythromycin inhibits bacterial protein synthesis by reversibly binding with their 50 S ribosomal subunit, thus blocking the formation of new peptide bonds. Erythromycin is classified as a bacteriostatic antibiotic. 

Clindamycin is a chlorine-substituted derivative of lincomycin. However it is more potent and is better absorbed from the gastrointestinal tract and has therefore replaced lincomycin in most situations. Clindamycin is in principle a bacteriostatic agent. Its indications are mainly limited to mixed anaerobic infections. As mentioned above it has a similar mechanism of action as erythromycin. It selectively inhibits bacterial protein synthesis by binding to the same 50s ribosomal subunits. Erythromycin and clindamycin can interfere with each other by competing for this receptor. Also cross-resistance with erythromycin frequently occurs. Resistance is rather chromosomal rather than plasmid mediated and is especially found in cocci and Clostridium difficile. 

Macrolides bind to the SOS ribosomal subunit of bacteria but not to the SOS mammalian ribosome this accounts for its selective toxicity. Binding to the ribosome occurs at a site near peptidyltransferase, with a resultant inhibition of translocation, peptide bond formation, and release of oligopeptidyl tRNA. However, unlike chloramphenicol, the macrolides do not inhibit protein synthesis by intact mitochondria, and this suggests that the mitochondrial membrane is not permeable to erythromycin. 

The lincosamide family of antibiotics includes lin-comycin (Lincocin) and clindamycin (Cleocin), both of which inhibit protein synthesis. They bind to the SOS ri-bosomal subunit at a binding site close to or overlapping the binding sites for chloramphenicol and erythromycin. They block peptide bond formation by interference at either the A or P site on the ribosome. Lincomycin is no longer available for human use in the United States. 

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