title: Entry of roxithromycin (RU 965), imipenem, cefotaxime, trimethoprim, and metronidazole into human polymorphonuclear leukocytes.
abstract: Entry of antibiotics into phagocytes is necessary for activity against intracellular organisms. Therefore, we examined the uptake of five of the newer antibiotics--roxithromycin (RU 965), imipenem, cefotaxime, trimethoprim, and metronidazole--by human polymorphonuclear leukocytes (PMN). Antibiotic uptake by PMN was determined by a velocity gradient centrifugation technique and expressed as the ratio of the cellular concentration of antibiotic to the extracellular concentration (C/E). Cefotaxime, like other beta-lactam antibiotics, was taken up poorly by phagocytes (C/E less than or equal to 0.3). The metronidazole concentration within PMN was similar to the extracellular level. Imipenem bound rapidly to phagocytes (C/E = 3), but cell-associated drug progressively declined during the incubation period. Trimethoprim was well concentrated by PMN (C/E = 9 to 13), and uptake was unexpectedly greater at 25 degrees C than at 37 degrees C. The most striking finding was that roxithromycin was more avidly concentrated by PMN (C/E = 34) than any other antibiotic we studied. Entry of roxithromycin into phagocytes was an active process and displayed saturation kinetics characteristic of a carrier-mediated membrane transport system. Ingestion of microbial particles by PMN slightly decreased the ability of these cells to accumulate roxithromycin (C/E = 24 to 31). These studies identified two antibiotics, trimethoprim and especially roxithromycin, which are markedly concentrated within human PMN and may prove useful in treatment of infections caused by susceptible intracellular organisms.
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002439:Cefotaxime / Q000493:pharmacokinetics; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015378:Imipenem; D066298:In Vitro Techniques; D007933:Leucomycins / Q000493:pharmacokinetics; D008795:Metronidazole / Q000493:pharmacokinetics; D009504:Neutrophils / Q000378:metabolism*; D013696:Temperature; D013845:Thienamycins / Q000493:pharmacokinetics; D014295:Trimethoprim / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D007933:Leucomycins; D013845:Thienamycins; D008795:Metronidazole; D015378:Imipenem; D014295:Trimethoprim; D002439:Cefotaxime