title: Changing patterns of hospital infections: implications for therapy. Changing concepts and new applications of antibiotic pharmacokinetics.
abstract: Antibiotics with high protein binding have a lower percentage of free drug available for tissue penetration than antibiotics with lower protein binding. High protein binding, however, may have a beneficial effect on drug distribution. The smaller volume of distribution and reduced glomerular filtration of highly bound agents result in higher serum levels that are sustained longer. Although intermittent and continuous dosing regimens produce similar areas under the concentration-versus-time curves for serum and tissue, intermittent dosing produces higher peak and potentially earlier effective antibiotic levels at the site of infection. The excretion of certain antibiotic agents in the bile may be related to hepatic protein binding, high molecular weight, or unique structural features. Biliary excretion is important not only for bile concentrations but also for dosage modification. Antibiotics with dual elimination by the kidney and biliary tract require minimal dosage modification unless there is concomitant hepatic and renal dysfunction. The third-generation cephalosporins provide good examples of how protein binding, tissue penetration, and excretory mechanisms can be used to alter pharmacokinetics advantageously.
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001646:Bile / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D001826:Body Fluids / Q000378:metabolism; D002511:Cephalosporins / Q000378:metabolism; D003428:Cross Infection / Q000188:drug therapy; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008970:Molecular Weight; D011485:Protein Binding; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D002511:Cephalosporins