Comparative uptake of rifampicin and rifapentine (DL473) by human neutrophils.
Rifapentine, a new cyclopentyl rifamycin, was weight for weight less active than rifampicin against Staphylococcus aureus. It was, however, equally effective at reducing the survival of Staph. aureus within human neutrophils even at concentrations below the conventionally determined MIC. The intracellular survival of antibiotic-resistant Staph. aureus was affected by neither agent. The bactericidal activity of neutrophil sonicates after exposure to both antibiotics showed that rifapentine was concentrated three-fold more than rifampicin. Uptake was temperature dependent and rapidly reached a plateau within 10 min. Uptake of rifampicin was unaffected by pH whereas that of rifapentine was reduced when the pH was lowered from 7.3 to 5. Studies with the metabolic inhibitors, sodium cyanide and potassium fluoride, suggested a minor role for both oxidative and glycolytic metabolism in this process. However, neither inhibitor had any demonstrable effect on the intracellular killing of Staph. aureus by either rifapentine or rifampicin.
D005459:Fluorides; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007460:Iodoacetamide / Q000494:pharmacology; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D009504:Neutrophils / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D017680:Potassium Compounds; D012293:Rifampin / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology; D012966:Sodium Cyanide / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D013696:Temperature; D013997:Time Factors
D017680:Potassium Compounds; C033320:potassium fluoride; D012966:Sodium Cyanide; D005459:Fluorides; D011188:Potassium; D012293:Rifampin; C018421:rifapentine; D007460:Iodoacetamide